2357-47-3

Basic information

• Product Name: 4-Fluoro-3-(trifluoromethyl)aniline
• Synonyms: α,α,α,4-Tetrafluoro-m-toluidine;5-Amino-2-fluorobenzotrifluoride, α,α,α,4-Tetrafluoro-m-toluidine;Benzenamine, 4-fluoro-3-(trifluoromethyl)-;4-Fluoro-3-(trifluoromethyl)-1-benzenamine;alpha,alpha,alpha,4-Tetrafluoro-m-toluidine,99%;4-fluoro-3-(trifluoromethyl)aniline4-fluoro-3-(trifluoromethyl)aniline;4-Fluoro-3-(trifluoromethyl)aniline,5-Amino-2-fluorobenzotrifluoride, α,α,α,4-Tetrafluoro-m-toluidine;4-Fluoro-3-(trifluor
• CAS NO: 2357-47-3
• Molecular Formula: C₇H₅F₄N
• Molecular Weight: 179.11
• EINECS: 219-095-7
• Product Categories: Miscellaneous;Trifluoromethylbenzene serise;Amines;blocks;FluoroCompounds;Fluorobenzene;Anilines, Aromatic Amines and Nitro Compounds;Aromatic Halides (substituted);Aniline;API intermediates
• Mol File: 2357-47-3.mol
• Article Data: 4

Chemical Properties

• Boiling Point: 207-208 °C(lit.)
• Flash Point: 197 °F
• Appearance: clear light yellow liquid
• Density: 1.393 g/mL at 25 °C(lit.)
• Vapor Pressure: 0.22mmHg at 25°C
• Refractive Index: n20/D 1.466(lit.)
• Storage Temp.: 0-6°C
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: 3.43±0.10(Predicted)
• BRN: 641587
• CAS DataBase Reference: 4-Fluoro-3-(trifluoromethyl)aniline(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Fluoro-3-(trifluoromethyl)aniline(2357-47-3)
• EPA Substance Registry System: 4-Fluoro-3-(trifluoromethyl)aniline(2357-47-3)

Safety Data

• Hazard Codes: Xn,Xi,T
• Statements: 20/21/22-36/37/38-23-21/22
• Safety Statements: 26-36-45-36/37/39
• RIDADR: 2811
• WGK Germany: 3
• HazardClass: IRRITANT
• Hazardous Substances Data: 2357-47-3(Hazardous Substances Data)

Usage

Uses

4-Fluoro-3-(trifluoromethyl)aniline was used in the synthesis of well-defined rod-coil block copolymers of trifluoromethylated poly(phenylene oxide).

InChI:InChI=1/C7H6BrFO/c1-10-7-3-2-5(8)4-6(7)9/h2-4H,1H3

Synthetic route

3-trifluoromethylnitrobenzene (98-46-4) → 3-trifluoromethylaniline (98-16-8) + 4-Fluoro-3-trifluoromethylaniline (2357-47-3)

Conditions	Yield
With bismuth; hydrogen fluoride In dichloromethane Yield given;	A n/a B 13%
With bismuth; hydrogen fluoride In dichloromethane Yields of byproduct given;	A n/a B 13%

2-Fluoro-5-nitrobenzotrifluoride (400-74-8) → 4-Fluoro-3-trifluoromethylaniline (2357-47-3)

Conditions	Yield
With iron; ammonium chloride
With hydrogen; palladium on activated charcoal In acetic acid under 760 Torr;
With hydrogen; palladium on activated charcoal In acetic acid
With hydrogen; acetic acid; palladium on activated charcoal

4-methoxy-benzaldehyde (123-11-5) + 4-Fluoro-3-trifluoromethylaniline (2357-47-3) → C15H13F4NO (953428-91-6)

Conditions	Yield
With thiophene; hydrogen; palladium 10% on activated carbon In methanol; di-isopropyl ether	100%

m-bromobenzoic acid (585-76-2) + 4-Fluoro-3-trifluoromethylaniline (2357-47-3) → 3-bromo-N-(4-fluoro-3-(trifluoromethyl)phenyl)benzamide

Conditions	Yield
With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 0 - 20℃; for 16h;	100%

4-chloro-6-(2-phenylethyl)-7H-pyrrolo[2,3-d]pyrimidine (1228352-77-9) + 4-Fluoro-3-trifluoromethylaniline (2357-47-3) → N-[4-fluoro-3-(trifluoromethyl)phenyl]-6-(2-phenylethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (1228352-65-5)

Conditions	Yield
With hydrogenchloride In water; isopropyl alcohol for 3h; Reflux;	95%

N-[4-chloro-6-(2-pyridin-2-ylethyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]-2,2-dimethylpropanamide (514225-32-2) + 4-Fluoro-3-trifluoromethylaniline (2357-47-3) → N-{4-[(3-trifluoromethyl,4-fluorophenyl)amino]-6-(2-pyridin-2-yl-ethyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl}-2,2-dimethylpropanamide (1424329-11-2)

Conditions	Yield
With hydrogenchloride In water; isopropyl alcohol for 3h; Reflux;	95%

2,2-dimethylsuccinic anhydride (17347-61-4) + 4-Fluoro-3-trifluoromethylaniline (2357-47-3) → 4-[[4-fluoro-3-(trifluoromethyl)phenyl]amino]-2,2-dimethyl-4-oxobutanoic acid

Conditions	Yield
In tetrahydrofuran at 20℃; for 12h;	93%

ethyl 1,3,5-trimethylpyrrole-2-carboxylate (55770-79-1) + 4-Fluoro-3-trifluoromethylaniline (2357-47-3) → N-[4-fluoro-3-(trifluoromethyl)phenyl]-1,3,5-trimethylpyrrole-2-carboxamide

Conditions	Yield
With lithium hexamethyldisilazane In tetrahydrofuran at 0 - 20℃; Inert atmosphere;	93%

4-(4-formyl-3-phenyl-1H-pyrazol-1-yl)benzoic acid + 4-Fluoro-3-trifluoromethylaniline (2357-47-3) → C24H17F4N3O2

Conditions	Yield
Stage #1: 4-(4-formyl-3-phenyl-1H-pyrazol-1-yl)benzoic acid; 4-Fluoro-3-trifluoromethylaniline In methanol for 12h; Reflux; Stage #2: With sodium tetrahydroborate In methanol at 0 - 20℃; for 12h;	90%

4-Fluoro-3-trifluoromethylaniline (2357-47-3) + 4-chloro-7-methoxy-6-(3-morpholinopropoxy)quinazoline (199327-59-8) → 4-[(4-fluoro-3-trifluoromethylphenyl)amino]-6-[3-(morpholin-4-yl)propyloxy]-7-methoxyquinazoline

Conditions	Yield
With acetic acid at 80℃; for 7h;	89%

α-Isocyanatobuttersaeure-methylester (54213-21-7) + 4-Fluoro-3-trifluoromethylaniline (2357-47-3) → 2-[3-(4-Fluoro-3-trifluoromethyl-phenyl)-ureido]-2-methyl-propionic acid methyl ester (92668-50-3)

Conditions	Yield
	88%

N-hydroxy-4-[(3-methoxypropyl)amino]-1,2,5-oxadiazole-3-carboximidoyl chloride + 4-Fluoro-3-trifluoromethylaniline (2357-47-3) → N-[4-fluoro-3-(trifluoromethyl)phenyl]-N'-hydroxy-4-[(3-methoxypropyl)amino]-1,2,5-oxadiazole-3-carboximidamide

Conditions	Yield
	87%

sodium phenoxide (139-02-6) + 4-Fluoro-3-trifluoromethylaniline (2357-47-3) → 4'-hydroxy-4-fluoro-3-(trifluoromethyl)azobenzene (221296-95-3)

Conditions	Yield
Stage #1: 4-Fluoro-3-trifluoromethylaniline With hydrogenchloride; sodium nitrite In water at 0℃; Stage #2: sodium phenoxide In water at 20℃; for 2h;	86%

3-(1,1-dimethyl-2-methylthioethylimino)-4-iodo-3H-isobenzofuran-1-one + 4-Fluoro-3-trifluoromethylaniline (2357-47-3) → N2-[1,1-dimethyl-2-(methylthio)ethyl]-3-iodo-N1-[4-fluoro-3-(trifluoromethyl)phenyl]-1,2-benzenedicarboxamide (1253787-09-5)

Conditions	Yield
In dichloromethane Cooling with ice;	86%

allyltributylstanane (24850-33-7) + 4-Fluoro-3-trifluoromethylaniline (2357-47-3) + Cyclopropanecarboxaldehyde (1489-69-6) → (1-cyclopropyl-but-3-enyl)(4-fluoro-3-trifluoromethylphenyl)amine (1281881-49-9)

Conditions	Yield
With trifluoroacetic acid In acetonitrile at 25℃; for 0.5h; Inert atmosphere;	85%

4-Fluoro-3-trifluoromethylaniline (2357-47-3) + [1,4]naphthoquinone (130-15-4) → 2-((4-fluoro-3-(trifluoromethyl)phenyl)amino)naphthalene-1,4-dione

Conditions	Yield
With cerium(III) chloride heptahydrate In ethanol at 20℃; for 12h;	85%

chlorosulfonyl-acetic acid methyl ester (56146-83-9) + 4-Fluoro-3-trifluoromethylaniline (2357-47-3) → 2-[N-(4-fluoro-3-trifluoromethylphenyl)sulfamoyl]-acetic acid methyl ester

Conditions	Yield
In pyridine; 1,1-dichloroethane	84.35%
With pyridine In dichloromethane

4-Fluoro-3-trifluoromethylaniline (2357-47-3) + 4-amino-N-hydroxy-1,2,5-oxadiazole-3-carboximidamidoyl chloride (147085-13-0) → 4-amino-N-[4-fluoro-3-(trifluoromethyl)phenyl]-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide

Conditions	Yield
With sodium hydrogencarbonate In tetrahydrofuran at 45℃; for 3.16667h; Reflux;	84%

4-chloro-6-(2-phenylethyl)-7H-pyrrolo[2,3-d]pyrimidin-2-amine (1037599-92-0) + 4-Fluoro-3-trifluoromethylaniline (2357-47-3) → C21H17F4N5 (1037599-89-5)

Conditions	Yield
With hydrogenchloride In isopropyl alcohol for 4h; Heating;	82%

1-chloro-4-phenylthiomethylphthalazine (929613-64-9) + 4-Fluoro-3-trifluoromethylaniline (2357-47-3) → 1-(4-fluoro-3-trifluoromethylanilino)-4-phenylthiomethylphthalazine

Conditions	Yield
In isopropyl alcohol at 50℃; for 3h;	81%

1-chloro-4-(3,4-difluorophenyl)thiomethylphthalazine (929613-76-3) + 4-Fluoro-3-trifluoromethylaniline (2357-47-3) → 1-(4-fluoro-3-trifluoromethylanilino)-4-(3,4-difluorophenylthiomethyl)phthalazine (929613-69-4)

Conditions	Yield
In isopropyl alcohol at 50℃; for 3h;	80%

1,4-diphenyl-1,3-butadiyne (886-66-8) + 4-Fluoro-3-trifluoromethylaniline (2357-47-3) → 1-(4-fluoro-3-(trifluoromethyl)phenyl)-2,5-diphenyl-1H-pyrrole

Conditions	Yield
With copper(l) chloride In N,N-dimethyl-formamide for 48h; Reflux; Inert atmosphere;	80%

3,5-dimethylaminoaniline (108-69-0) + 4-Fluoro-3-trifluoromethylaniline (2357-47-3) → [(4-fluoro-3-trifluoromethylphenyl)aminocarbonylmethyl]chloride (40992-76-5)

Conditions	Yield
With sodium hydroxide In dichloromethane; water for 18h;	79%

4-Fluoro-3-trifluoromethylaniline (2357-47-3) → [(4-fluoro-3-trifluoromethylphenyl)aminocarbonylmethyl]chloride (40992-76-5)

Conditions	Yield
	79%

4-Fluoro-3-trifluoromethylaniline (2357-47-3) + malononitrile (109-77-3) → N-(4-fluoro-3-(trifluoromethyl)phenyl)carbohydrazonoyl dicyanide

Conditions	Yield
Stage #1: 4-Fluoro-3-trifluoromethylaniline With hydrogenchloride; sodium nitrite In water for 1.5h; Cooling with ice; Stage #2: malononitrile With sodium acetate In water at 0℃; for 2h;	78%

2-chloro-3-methoxy-1,4-naphthoquinone (15707-32-1) + 4-Fluoro-3-trifluoromethylaniline (2357-47-3) → 2-((4-fluoro-3-(trifluoromethyl)phenyl)amino)-3-methoxynaphthalene-1,4-dione

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); potassium tert-butylate; XPhos In toluene at 130℃; for 0.5h; Buchwald-Hartwig Coupling; Microwave irradiation; Sealed tube; Inert atmosphere;	78%

4-(4-aminophenoxy)-N-methylpyridine-2-carboxamide (284462-37-9) + 4-Fluoro-3-trifluoromethylaniline (2357-47-3) + 1,1'-carbonyldiimidazole (530-62-1) → 4-(4-(3-(4-fluoro-3-(trifluoromethyl)phenyl)ureido)phenoxy)-N-methylpicolinamide

Conditions	Yield
Stage #1: 4-Fluoro-3-trifluoromethylaniline; 1,1'-carbonyldiimidazole In dichloromethane at 20℃; for 16.1667h; Stage #2: 4-(4-aminophenoxy)-N-methylpyridine-2-carboxamide In dichloromethane for 12h;	77%

N-(4-chlorophenylsulphonyl)aziridine (50707-38-5) + 4-Fluoro-3-trifluoromethylaniline (2357-47-3) → N-(2-{[4-fluoro-3-(trifluormethyl)phenyl]amino}-ethyl)-4-chlorobenzene sulfonamide

Conditions	Yield
Stage #1: N-(4-chlorophenylsulphonyl)aziridine; 4-Fluoro-3-trifluoromethylaniline With silica gel In water for 1.5h; Sonication; Stage #2: In water at 20℃; for 20h;	77%

2-(3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamido)acetic acid (1423020-38-5) + 4-Fluoro-3-trifluoromethylaniline (2357-47-3) → 3-bromo-1-(3-chloropyridin-2-yl)-N-(2-((4-fluoro-3-(trifluoromethyl)phenyl)amino)-2-oxoethyl)-1H-pyrazole-5-carboxamide (1423020-29-4)

Conditions	Yield
With triethylamine; trichlorophosphate In acetonitrile for 2h; Reflux;	76%

C9H6ClNO3S2 + 4-Fluoro-3-trifluoromethylaniline (2357-47-3) → N-(2-chloro-4-methylsulfonylbenzoyl)-N'-(3-trifluoromethyl-4-fluorophenyl)thiourea

Conditions	Yield
at 20℃;	76%

bis(trichloromethyl) carbonate (32315-10-9) + 2-amino-4-chloro-7-methyl-7H-pyrrolo<2,3-d>pyrimidine (90065-71-7) + 4-Fluoro-3-trifluoromethylaniline (2357-47-3) → 1-(4-chloro-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-3-(4-fluoro-3-(trifluoromethyl)phenyl)urea

Conditions	Yield
Stage #1: bis(trichloromethyl) carbonate; 2-amino-4-chloro-7-methyl-7H-pyrrolo<2,3-d>pyrimidine With triethylamine In 1,4-dioxane at 0 - 20℃; for 5h; Inert atmosphere; Stage #2: 4-Fluoro-3-trifluoromethylaniline at 20℃;	75%

5-chloro-2-hydroxybenzoic acid (321-14-2) + 4-Fluoro-3-trifluoromethylaniline (2357-47-3) → 5-chloro-N-(4-fluoro-3-(trifluoromethyl)phenyl)-2-hydroxybenzamide

Conditions	Yield
	72.1%
With pyridine; phosphorus trichloride In toluene for 12h; Inert atmosphere; Reflux;

Upstream product

• 98-46-4 3-trifluoromethylnitrobenzene 
• 400-74-8 2-Fluoro-5-nitrobenzotrifluoride 

Downstream Products

• 1998-81-8 N-<4-Fluor-3-trifluormethyl-phenyl>-carbamidsaeureisopropylester 
• 77140-72-8 α,α,α,4-Tetrafluor-m-tolylcarbamidsaeurephenylester 
• 620-50-8 N,N'-di(m-tolyl)urea 
• 1227-44-7 N,N'-bis(4-methoxyphenyl)urea 
• 35685-21-3 1-(4-Fluoro-3-trifluoromethyl-phenyl)-3-(4-methoxy-phenyl)-urea 
• 882678-71-9 N-(4-fluoro-3-(trifluoromethyl)phenyl)-3-iodo-4-methylbenzamide 
• 929212-92-0 1-fluoro-4-methylsulfanyl-2-trifluoromethyl-benzene 
• 1067997-16-3 C₁₆H₁₀ClF₅N₂O₃ 
• 1228352-65-5 N-[4-fluoro-3-(trifluoromethyl)phenyl]-6-(2-phenylethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine 

Relevant articles and documents

Design and synthesis of novel 7-heterocycle-6-trifluoromethyl-3- oxoquinoxaline-2-carboxylic acids bearing a substituted phenyl group as superior AMPA receptor antagonists with good physicochemical properties

We describe the design, synthesis, and physicochemical and biological properties of a novel series of 7-heterocycle-6-trifluoromethyl-3- oxoquinoxaline-2-carboxylic acids bearing a substituted phenyl group joined through a urethane or urea linkage to the heterocycle at the 7 position. Introduction of the trifluoromethyl group at the 6 position conferred good biological activity, including neuroprotective effects, as well as good physicochemical properties. In terms of α-amino-3-hydroxy-5- methylisoxazole propionate receptor (AMPA-R) affinity, a urea linkage was equivalent to a urethane linkage and a pyrrole ring at the 7 position reduced affinity in comparison with an imidazole ring. Among this series, compound 14h (KRP-199), which has a 4-carboxyphenyl group joined through a urethane linkage to a 7-imidazolyl heterocycle, was found to possess high potency and selectivity for the AMPA-R in vitro and to exhibit good neuroprotective effects in vivo. Furthermore, the compound showed good physicochemical properties, including stability to light and good solubility in aqueous solutions.

The Bamberger reaction in hydrogen fluoride: the use of mild reductive metals for the preparation of fluoroaromatic amines

The reduction of nitroaromatic compounds by various metals (tin, lead, bismuth) in liquid hydrogen fluoride under an inert atmosphere leads to fluoroaromatic amines, in accord with the Bamberger reaction.Generally, a co-solvent such as pentane or methylene chloride is used.Some non-fluorinated arylamines are also formed by a competitive direct reduction of the N-arylhydroxylamine intermediate.Of the mild reductive metals studied, bismuth was the most selective. - Keywords: Bamberger reaction; Hydrogen fluoride; Mild reductive metals; Fluoroaromatic amines; NMR spectroscopy