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

Description

4-Fluorobenzotrifluoride, also known as α,α,α-trifluorotoluene, is an aromatic compound belonging to the family of fluorinated aromatics. It is characterized by the presence of a fluorine atom at the para position and three fluorine atoms on the benzene ring, which imparts unique chemical and physical properties to the molecule. As a clear, colorless to light yellow liquid, 4-Fluorobenzotrifluoride is known for its reactivity in various chemical reactions, making it a versatile building block in the synthesis of a wide range of organic compounds.

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 
• 352-34-1 4-fluoro-1-iodobenzene 
• 1765-93-1 4-fluoroboronic acid 

Downstream Products

• 115029-23-7 2-fluoro-5-(trifluoromethyl)benzoic acid 
• 125923-59-3 methyl difluoro(4-fluorophenyl)acetate 
• 146137-78-2 2-fluoro-5-trifluoromethylbenzaldehyde 
• 287952-08-3 tert-butyl 4-(4-(trifluoromethyl)phenoxy)piperidine-1-carboxylate 
• 26771-69-7 2-methoxy-1-(4-(trifluoromethyl)phenyl)ethan-1-one 
• 352-32-9 p-fluorotoluene 
• 53451-89-1 4-methoxyphenoxy-4-trifluoromethylphenyl ether 
• 146137-92-0 methyl 5-(trifluoromethyl)benzo[b]thiophene-2-carboxylate 
• 78748-23-9 3-(4-trifluoromethylphenoxy)aniline 
• 93291-44-2 1-(4-(4-(trifluoromethyl)phenoxy)phenyl)ethan-1-one 
• 299206-62-5 4-[4-(4-trifluoromethylphenoxy)phenyl]-1H-imidazole, hydrochloride salt 

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.

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%.

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.