402-44-8

Basic information

• Product Name: 4-Fluorobenzotrifluoride
• Synonyms: alpha,alpha,alpha,p-Tetrafluorotoluene;benzene,1-fluoro-4-(trifluoromethyl)-;p-(Trifluoromethyl)fluorobenzene;p-alpha,alpha,alpha-Tetrafluoro toluene;p-Fluorotrifluoromethylbenzene;Toluene, p,alpha,alpha,alpha-tetrafluoro-;toluene,p,α,α,α-tetrafluoro-;π,a,a,a-tetrafluorotoluene
• CAS NO: 402-44-8
• Molecular Formula: C₇H₄F₄
• Molecular Weight: 164.1
• EINECS: 206-944-1
• Product Categories: Trifluoromethylbenzene serise;Fluorobenzene;Aromatic Hydrocarbons (substituted) & Derivatives
• Mol File: 402-44-8.mol
• Article Data: 61

Chemical Properties

• Melting Point: −42-−41.7 °C(lit.)
• Boiling Point: 102-105 °C(lit.)
• Flash Point: 51 °F
• Appearance: Clear colorless/Liquid
• Density: 1.293 g/mL at 25 °C(lit.)
• Vapor Pressure: 35.8mmHg at 25°C
• Refractive Index: n20/D 1.401(lit.)
• Storage Temp.: Refrigerator
• Water Solubility: Slightly soluble in water.
• BRN: 1909390
• CAS DataBase Reference: 4-Fluorobenzotrifluoride(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Fluorobenzotrifluoride(402-44-8)
• EPA Substance Registry System: 4-Fluorobenzotrifluoride(402-44-8)

Safety Data

• Hazard Codes: F,Xi,F+
• Statements: 11-36/37/38
• Safety Statements: 16-26-33-24/25-7/9
• RIDADR: UN 1993 3/PG 2
• WGK Germany: 3
• TSCA: T
• HazardClass: 3
• PackingGroup: II
• Hazardous Substances Data: 402-44-8(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
4-Fluorobenzotrifluoride is used as a synthetic intermediate for the development of various pharmaceutical compounds. Its unique reactivity and structural features make it a valuable component in the synthesis of potent inhibitors, such as (S)-fluoxetine, which is a well-known inhibitor of neuronal serotonin-uptake. This application is particularly important in the treatment of depression and other mood disorders.
Used in Chemical Synthesis:
In the field of chemical synthesis, 4-Fluorobenzotrifluoride serves as a key building block for the creation of various organic compounds. Its reactivity in nucleophilic aromatic substitution reactions allows for the synthesis of complex molecules, such as 2,2'-bis(trifluoromethylphenoxy)biphenyl, which can be further utilized in the development of advanced materials and pharmaceuticals.
Used in the Synthesis of 1-aryloxy-2-substituted aminomethyltetrahydronaphthalene Derivatives:
4-Fluorobenzotrifluoride is also employed in the synthesis of 1-aryloxy-2-substituted aminomethyltetrahydronaphthalene derivatives, which are important compounds with potential applications in various industries, including pharmaceuticals and materials science. The unique properties of 4-Fluorobenzotrifluoride enable the efficient synthesis of these derivatives, contributing to the development of novel compounds with diverse applications.

Synthesis Reference(s)

Tetrahedron, 49, p. 8129, 1993 DOI: 10.1016/S0040-4020(01)88032-7

InChI:InChI=1/C7H4F4/c8-6-3-1-5(2-4-6)7(9,10)11/h1-4H

Upstream product

• 402-42-6 4-fluoro-1-trichloromethylbenzene 
• 56-23-5 tetrachloromethane 
• 462-06-6 fluorobenzene 
• 455-14-1 4-trifluoromethylphenylamine 
• 98-08-8 α,α,α-trifluorotoluene 
• 658-75-3 p-fluorophenyl trifluoroacetate 
• 312-75-4 trimethyl(4-trifluoromethylphenyl)silane 
• 71940-14-2 p-Trifluoromethylphenyllead(IV) triacetate 
• 128796-45-2 2,4,6-tris-(4-trifluoromethylphenyl)boroxine 
• 55642-42-7 bis(trifluoromethyl)tellurium 
• 402-54-0 p-nitrobenzotrifluoride 
• 352-32-9 p-fluorotoluene 
• 546-67-8 lead(IV) tetraacetate 
• 109-63-7 trifluoroborane diethyl ether 

Downstream Products

• 367-86-2 1-fluoro-2-nitro-4-trifluoromethyl-benzene 
• 115029-23-7 2-fluoro-5-(trifluoromethyl)benzoic acid 
• 125923-59-3 methyl difluoro(4-fluorophenyl)acetate 
• 128470-60-0 Benzyl-methyl-[1-(4-trifluoromethyl-phenoxy)-indan-2-ylmethyl]-amine 
• 100568-02-3 (S)-fluoxetine 
• 69584-96-9 1'-methyl-1-[(4-trifluoromethyl)-phenyl]spiro[indoline-3,4'-piperidine] 
• 24154-20-9 p-Fluorphenyldifluorcarbenium-Ion 
• 146137-78-2 2-fluoro-5-trifluoromethylbenzaldehyde 
• 402-42-6 4-fluoro-1-trichloromethylbenzene 
• 24572-48-3 1-fluoro-4-(tribromomethyl)benzene 
• 16237-51-7 1-Phenyl-1--aethan 
• 157911-66-5 pyrimidin-5-yl-(4-trifluoromethyl-phenyl)-amine 
• 32445-87-7 2-methyl-2-(4-(trifluoromethyl)phenyl)propanenitrile 
• 287952-08-3 tert-butyl 4-(4-(trifluoromethyl)phenoxy)piperidine-1-carboxylate 

Relevant articles and documents

Cross-Coupling through Ag(I)/Ag(III) Redox Manifold

In ample variety of transformations, the presence of silver as an additive or co-catalyst is believed to be innocuous for the efficiency of the operating metal catalyst. Even though Ag additives are required often as coupling partners, oxidants or halide scavengers, its role as a catalytically competent species is widely neglected in cross-coupling reactions. Most likely, this is due to the erroneously assumed incapacity of Ag to undergo 2e? redox steps. Definite proof is herein provided for the required elementary steps to accomplish the oxidative trifluoromethylation of arenes through AgI/AgIII redox catalysis (i. e. CEL coupling), namely: i) easy AgI/AgIII 2e? oxidation mediated by air; ii) bpy/phen ligation to AgIII; iii) boron-to-AgIII aryl transfer; and iv) ulterior reductive elimination of benzotrifluorides from an [aryl-AgIII-CF3] fragment. More precisely, an ultimate entry and full characterization of organosilver(III) compounds [K]+[AgIII(CF3)4]? (K-1), [(bpy)AgIII(CF3)3] (2) and [(phen)AgIII(CF3)3] (3), is described. The utility of 3 in cross-coupling has been showcased unambiguously, and a large variety of arylboron compounds was trifluoromethylated via [AgIII(aryl)(CF3)3]? intermediates. This work breaks with old stereotypes and misconceptions regarding the inability of Ag to undergo cross-coupling by itself.

Fluorination of arylboronic esters enabled by bismuth redox catalysis

Bismuth catalysis has traditionally relied on the Lewis acidic properties of the element in a fixed oxidation state. In this paper, we report a series of bismuth complexes that can undergo oxidative addition, reductive elimination, and transmetallation in a manner akin to transition metals. Rational ligand optimization featuring a sulfoximine moiety produced an active catalyst for the fluorination of aryl boronic esters through a bismuth (III)/bismuth (V) redox cycle. Crystallographic characterization of the different bismuth species involved, together with a mechanistic investigation of the carbonfluorine bond-forming event, identified the crucial features that were combined to implement the full catalytic cycle.

Oxidatively Induced Aryl-CF3 Coupling at Diphosphine Nickel Complexes

This communication describes the synthesis of a series of diphosphine NiII(Ph)(CF3) complexes and studies of their reactivity toward oxidatively induced Ph-CF3 bond-forming reductive elimination. Treatment of these complexes with the one-electron outer-sphere oxidant ferrocenium hexafluorophosphate (FcPF6) affords benzotrifluoride, but the yield varies dramatically as a function of diphosphine ligand. Diphosphines with bite angles of less than 92° afforded 3. In contrast, those with bite angles between 95 and 102° formed PhCF3 in yields ranging from 62 to 77%.

Mechanism of Photoredox-Initiated C-C and C-N Bond Formation by Arylation of IPrAu(I)-CF3 and IPrAu(I)-Succinimide

Herein, we report on the photoredox-initiated gold-mediated C(sp2)-CF3 and C(sp2)-N coupling reactions. By adopting gold as a platform for probing metallaphotoredox catalysis, we demonstrate that cationic gold(III) complexes are the key intermediates of the C-C and C-N coupling reactions. The high-valent gold(III) intermediates are accessed by virtue of photoredox catalysis through a radical chain process. In addition, the bond-forming step of the coupling reactions is the reductive elimination from cationic gold(III) intermediates, which is supported by isolation and crystallographic characterization of key Au(III) intermediates.

The Difluoromethylated Organogold(III) Complex cis-[Au(PCy3)(4-F-C6H4)(CF2H)(Cl)]: Preparation, Characterization, and Its C(sp2)-CF2H Reductive Elimination

The preparation of the difluoromethylated organogold(III) complex cis-[Au(PCy3)(4-F-C6H4)(CF2H)(Cl)] (3) and its Ar-CF2H reductive elimination are described. In the presence of 1.0 equiv of AgSbF6 or AgPF6, compound 3 underwent a quantitative Ar-CF2H reductive elimination in less than 1.0 min at 25 °C, while the lack of silver salt resulted in Ar-CF2H reductive elimination from complex 3 in 1,1,2,2-tetrachloroethane (CCl2HCCl2H) after 80 min at 115 °C to afford the elimination product p-F-PhCF2H (4) and (Cy3P)Au(Cl) in quantitative yields. On the basis of the mechanistic studies of the kinetics of the reaction and DFT calculation, a concerted Ar-CF2H bond-forming pathway for the Ar-CF2H reductive elimination from organogold(III) complex 3 is proposed.

METHOD FOR AROMATIC FLUORINATION

Disclosed is a fluorination method comprising providing an aryl fluorosuifonate and a fluorinating reagent to a reaction mixture; and reacting the aryl fluorosuifonate and the fluorinating reagent to provide a fluorinated aryl species. Also disclosed is a fluorination method comprising providing, a salt comprising a cation and an aryloxyiate, and SO2F2 to a reaction mixture; reacting the SO2F2 and the ammonium salt to provide a fluorinated aryl species. Further disclosed a fluorination method comprising providing a compound having the structure Ar-OH to a reaction mixture; where A is an aryl or heteroaryl; providing SO2F2 to the reaction mixture; providing a fluorinating reagent to the reaction mixture; reacting the SO2F2, the fluorinating reagent and the compound having the structure Ar-OH to provide a fluorinated aryl species having the structure Ar-F.

Nucleophilic deoxyfluorination of phenols via aryl fluorosulfonate intermediates

This report describes a method for the deoxyfluorination of phenols with sulfuryl fluoride (SO2F2) and tetramethylammonium fluoride (NMe4F) via aryl fluorosulfonate (ArOFs) intermediates. We first demonstrate that the reaction of ArOFs with NMe4F proceeds under mild conditions (often at room temperature) to afford a broad range of electronically diverse and functional group-rich aryl fluoride products. This transformation was then translated to a one-pot conversion of phenols to aryl fluorides using the combination of SO2F2 and NMe4F. Ab initio calculations suggest that carbon-fluorine bond formation proceeds via a concerted transition state rather than a discrete Meisenheimer intermediate.

Stoichiometric and Catalytic Aryl-Perfluoroalkyl Coupling at Tri-tert-butylphosphine Palladium(II) Complexes

This Communication describes studies of Ph-RF (RF = CF3 or CF2CF3) coupling at Pd complexes of general structure (PtBu3)PdII(Ph)(RF). The CF3 analogue participates in fast Ph-CF3 coupling (II complex. Furthermore, they show that this undesired pathway can be circumvented by changing from a CF3 to a CF2CF3 ligand. Ultimately, the insights gained from stoichiometric studies enabled the identification of Pd(PtBu3)2 as a catalyst for the Pd-catalyzed cross-coupling of aryl bromides with TMSCF2CF3 to afford pentafluoroethylated arenes.

Method for synthesizing trifluoromethyl aromatic compounds

The invention aims to provide a method for converting arylamine into trifluoromethyl aromatic compounds under simple conditions. The trifluoromethyl aromatic compounds can be widely applied to the fields of pesticides, medicines, organic materials and the like. The method is characterized by comprising steps of (1), synthesizing Toni reagents alpha from sodium periodate, 2-iodobenzoic acid, acetic anhydride, cesium fluoride and Ruppert reagents; (2), dissolving the arylamine and hydrochloric acid in 1, 2-dichloroethane, stirring the arylamine, the hydrochloric acid and the 1, 2-dichloroethane for 5-10 min to obtain mixtures, adding tert-butyl nitrite into the mixtures under low-temperature conditions, carrying out stirring reaction for 30-60 min to obtain reaction products, adding tetrafluoroboric acid tetra-acetonitrile copper, the Toni reagents alpha and sodium bicarbonate into the reaction products and carrying micro-heat reaction for 10-20 hours; sequentially filtering, washing and drying reaction liquid after reaction is completely carried out and carrying out column chromatography separation and purification on the reaction liquid to obtain target products. The method has the advantage that the trifluoromethyl aromatic compounds can be widely applied to the fields of pesticides, medicines, organic materials and the like.

Copper-catalysed synthesis of trifluoromethyl(hetero)arenes from di(hetero)aryl-λ3-iodanes

An efficient synthesis of trifluoromethylated (hetero)arenes has been achieved through the regioselective copper-catalyzed trifluoromethylation of di(hetero)aryl-λ3-iodanes, employing readily available trifluoromethyltrimethylsilane. The reaction works well for both symmetrical and unsymmetrical di(hetero)aryl-λ3-iodanes with good regioselectivity and also tolerates diverse functional groups such as bromo, iodo, cyano, nitro, ester, ketone and enolizable ketone.