194853-86-6

Basic information

• Product Name: 4-Fluoro-2-trifluoromethylbenzonitrile
• Synonyms: 2-TRIFLUOROMETHYL-4-FLUOROBENZONITRILE;2-CYANO-5-FLUOROBENZOTRIFLUORIDE;4-FLUORO-2-(TRIFLUOROMETHYL)BENZONITRILE;2-Cyano-5-fluorobenzotrifluoride~alpha,alpha,alpha,4-Tetrafluoro-o-tolunitrile;4-Fluoro-2-(Trifluoromethyl)Benzonitrile/A,A,A,4-Tetrafluoro-O-Tolunitrile/2-Cyano-5-Fluorobenzotrifluoride;à,à,à,4-tetrafluoro-o-tolunitrile;4-Fluoro-2-(trifluoromethyl)benzonitrile 97%;4-Fluoro-2-(trifluoromethyl)benzonitrile97%
• CAS NO: 194853-86-6
• Molecular Formula: C₈H₃F₄N
• Molecular Weight: 189.11
• EINECS: -0
• Product Categories: Benzene derivatives;Aromatic Nitriles;Benzoic acid;Benzotrifluoride Series;Fluorine series
• Mol File: 194853-86-6.mol
• Article Data: 2

Chemical Properties

• Melting Point: 43-45°C
• Boiling Point: 53°C 15mm
• Flash Point: 194-196°C
• Appearance: white or off white crystalline
• Density: 1,35 g/cm3
• Vapor Pressure: 0.269mmHg at 25°C
• Refractive Index: 1.443
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: Chloroform (Sparingly), Methanol (Slightly)
• Water Solubility: Insoluble in water. Solubility in methanol is almost transparent.
• CAS DataBase Reference: 4-Fluoro-2-trifluoromethylbenzonitrile(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Fluoro-2-trifluoromethylbenzonitrile(194853-86-6)
• EPA Substance Registry System: 4-Fluoro-2-trifluoromethylbenzonitrile(194853-86-6)

Safety Data

• Hazard Codes: T,Xi,Xn
• Statements: 20/21/22-36/37/38-22
• Safety Statements: 26-36/37/39-45-36-36/37-23-9
• RIDADR: 3276
• HazardClass: 6.1
• PackingGroup: III
• Hazardous Substances Data: 194853-86-6(Hazardous Substances Data)

Usage

Chemical Properties

White solid

Uses

It is used as a pharmaceutical intermediate. It is also used for the synthesis of diphenylthioethers.

InChI:InChI=1/C8H3F4N/c9-6-2-1-5(4-13)7(3-6)8(10,11)12/h1-3H

Synthetic route

4-fluorobenzonitrile (1194-02-1) + trifluoroacetic acid (76-05-1) → 4-Fluoro-3-(trifluoromethyl)benzonitrile (67515-59-7) + 4-fluoro-2-(trifluoromethyl)benzonitrile (194853-86-6)

Conditions	Yield
With dipotassium peroxodisulfate; sulfuric acid; sodium carbonate; silver carbonate In dichloromethane at 120℃; for 10h; Schlenk technique; Sealed tube;

[(4-chlorophenyl)thio]pentafluorobenzene (16495-77-5) + C15H7F3N2O → 1-[(4-chlorophenyl)thio]-4-[(4-cyanophenyl)oxy]-2,3,5,6-tetrafluorobenzene + 4-fluoro-2-(trifluoromethyl)benzonitrile (194853-86-6)

Conditions	Yield
With bis[1,2-bis(diphenylphosphino)benzene]hydriderhodium(I) In chlorobenzene for 3h; Inert atmosphere; Reflux;	A n/a B 96%

5,5-dimethyl-imidazolidine-2,4-dione (77-71-4) + 4-fluoro-2-(trifluoromethyl)benzonitrile (194853-86-6) → 4-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-2-(trifluoromethyl)benzonitrile (143782-20-1)

Conditions	Yield
Stage #1: 5,5-dimethyl-imidazolidine-2,4-dione With potassium carbonate In N,N-dimethyl-formamide at 45℃; for 0.5h; Stage #2: 4-fluoro-2-(trifluoromethyl)benzonitrile In N,N-dimethyl-formamide for 5h; Heating;	79%
Stage #1: 5,5-dimethyl-imidazolidine-2,4-dione With potassium carbonate In N,N-dimethyl-formamide at 45℃; for 0.5h; Stage #2: 4-fluoro-2-(trifluoromethyl)benzonitrile In N,N-dimethyl-formamide for 5h;	79%
With potassium carbonate In N,N-dimethyl-formamide at 45℃; for 48h; Inert atmosphere;	74%

4-fluoro-2-(trifluoromethyl)benzonitrile (194853-86-6) → 4-mercapto-2-(trifluoromethyl)benzonitrile

Conditions	Yield
Stage #1: 4-fluoro-2-(trifluoromethyl)benzonitrile With sodium sulfide In N,N-dimethyl-formamide at 20℃; for 1h; Inert atmosphere; Stage #2: With hydrogenchloride; zinc In water Cooling with ice; Inert atmosphere;	85%
Stage #1: 4-fluoro-2-(trifluoromethyl)benzonitrile In dimethyl sulfoxide at 75℃; for 0.333333h; Stage #2: With sodiumsulfide nonahydrate In dimethyl sulfoxide at 75℃; for 2h;

cyclopropanemethylamine (2516-47-4) + 4-fluoro-2-(trifluoromethyl)benzonitrile (194853-86-6) → 4-[(cyclopropylmethyl)amino]-2-(trifluoromethyl)benzonitrile

Conditions	Yield
With potassium carbonate In acetonitrile at 55℃; for 12h;	99%
With potassium carbonate In acetonitrile at 55℃; for 12h;	99%

vanillin (121-33-5) + 4-fluoro-2-(trifluoromethyl)benzonitrile (194853-86-6) → 4-(4-formyl-2-methoxyphenoxy)-2-trifluoromethylbenzonitrile (1262328-60-8)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 95℃; for 5h;	97%
With lithium carbonate In dimethyl sulfoxide at 100℃; for 48h;	92%

4-fluoro-2-(trifluoromethyl)benzonitrile (194853-86-6) → 4-fluoro-3-iodo-2-(trifluoromethyl)benzonitrile (1539314-78-7)

Conditions	Yield
Stage #1: 4-fluoro-2-(trifluoromethyl)benzonitrile With lithium diisopropyl amide In tetrahydrofuran at -45℃; for 0.0666667h; Inert atmosphere; Stage #2: With 2-methyltetrahydrofuran; iodine at -45℃; for 0.00444444h; Inert atmosphere; regioselective reaction;	67%
Stage #1: 4-fluoro-2-(trifluoromethyl)benzonitrile With lithium diisopropyl amide In tetrahydrofuran at -45℃; for 0.5h; Stage #2: With iodine In tetrahydrofuran at -70 - -52℃; for 1h;	44.1%
Stage #1: 4-fluoro-2-(trifluoromethyl)benzonitrile With lithium diisopropyl amide In tetrahydrofuran at -45 - -40℃; for 0.5h; Stage #2: With iodine In tetrahydrofuran at -70 - -52℃; for 1h;	44.1%
Stage #1: 4-fluoro-2-(trifluoromethyl)benzonitrile With lithium diisopropyl amide In tetrahydrofuran at -45 - -40℃; for 0.5h; Stage #2: With iodine In tetrahydrofuran at -70 - -52℃; for 1h;	44.1%

9H,9′H-[3,3′]bicarbazole (1984-49-2) + 4-fluoro-2-(trifluoromethyl)benzonitrile (194853-86-6) → 4,4'-(9H,9'H-[3,3'-bicarbazole]-9,9'-diyl)bis(2-(trifluoromethyl)benzonitrile)

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide at 140℃; for 12h;	92%
With potassium carbonate In dimethyl sulfoxide at 140℃; for 12h; Inert atmosphere;	90%

5-bromoindoline (22190-33-6) + 4-fluoro-2-(trifluoromethyl)benzonitrile (194853-86-6) → C16H10BrF3N2

Conditions	Yield
Stage #1: 5-bromoindoline With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.5h; Stage #2: 4-fluoro-2-(trifluoromethyl)benzonitrile In N,N-dimethyl-formamide at 20℃; for 2h;	87.1%
Stage #1: 5-bromoindoline With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.5h; Stage #2: 4-fluoro-2-(trifluoromethyl)benzonitrile at 20℃; for 2h;

trans-4-hydroxycyclohexylamine (27489-62-9) + 4-fluoro-2-(trifluoromethyl)benzonitrile (194853-86-6) → 4-(4-cyano-3-trifluoromethyl-phenylamino)-cyclohexanol (1163268-86-7)

Conditions	Yield
With potassium carbonate In water; acetonitrile at 80℃; for 72h;	80%
With potassium carbonate In acetonitrile at 90℃;	33%

N-(n-propyl)-N-(cyclopropanemethyl)amine (26389-60-6) + 4-fluoro-2-(trifluoromethyl)benzonitrile (194853-86-6) → 4-[(cyclopropylmethyl)(propyl)amino]-2-(trifluoromethyl)benzonitrile

Conditions	Yield
Stage #1: N-(n-propyl)-N-(cyclopropanemethyl)amine; 4-fluoro-2-(trifluoromethyl)benzonitrile With polystyrene supported morpholine In dimethyl sulfoxide at 99℃; for 20h; Stage #2: With PS-isocyanate; PS-Trisamine scavenger reagent In dimethyl sulfoxide at 90℃; for 12h;	81%
With caesium carbonate In dimethyl sulfoxide at 90℃; for 3h;	81%

(3-((tetrahydro-2H-pyran-2-yl)oxy)phenyl)methanol (925416-98-4) + 4-fluoro-2-(trifluoromethyl)benzonitrile (194853-86-6) → C20H18F3NO3 (925416-99-5)

Conditions	Yield
With sodium hydride In 1,2-dimethoxyethane at 0 - 60℃;	94%

D-allo-threonine (24830-94-2) + 4-fluoro-2-(trifluoromethyl)benzonitrile (194853-86-6) → (2R,3R)-2-(4-cyano-3-(trifluoromethyl)phenylamino)-3-hydroxybutanoic acid (1182368-21-3)

Conditions	Yield
Stage #1: D-allo-threonine; 4-fluoro-2-(trifluoromethyl)benzonitrile With potassium carbonate In dimethyl sulfoxide at 20 - 75℃; Stage #2: With citric acid In water	100%

(R)-(-)-β-hydroxyvaline (2280-48-0) + 4-fluoro-2-(trifluoromethyl)benzonitrile (194853-86-6) → C13H13F3N2O3 (1354339-84-6)

Conditions	Yield
Stage #1: (R)-(-)-β-hydroxyvaline; 4-fluoro-2-(trifluoromethyl)benzonitrile With potassium carbonate In dimethyl sulfoxide at 85℃; for 96h; Stage #2: With citric acid In water	98%

4-Iodophenol (540-38-5) + 4-fluoro-2-(trifluoromethyl)benzonitrile (194853-86-6) → 4-(4-iodophenoxy)-2-(trifluoromethyl)benzonitrile (1097084-96-2)

Conditions	Yield
With sodium carbonate In N,N-dimethyl-formamide at 100℃; for 20h;	69%
With sodium carbonate In N,N-dimethyl-formamide at 100℃;

4-(4-fluorobenzyl)-3,5-dimethyl-1H-pyrazole (1189140-61-1) + 4-fluoro-2-(trifluoromethyl)benzonitrile (194853-86-6) → 4-[4-(4-fluorobenzyl)-3,5-dimethyl-1H-pyrazol-1-yl]-2-(trifluoromethyl)benzonitrile (1189135-45-2)

Conditions	Yield
Stage #1: 4-(4-fluorobenzyl)-3,5-dimethyl-1H-pyrazole With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.5h; Stage #2: 4-fluoro-2-(trifluoromethyl)benzonitrile In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 20h;	87%

diethyl malonate (105-53-3) + 4-fluoro-2-(trifluoromethyl)benzonitrile (194853-86-6) → diethyl 2-[4-cyano-3-(trifluoromethyl)phenyl]propanedioate

Conditions	Yield
Stage #1: diethyl malonate With caesium carbonate In N,N-dimethyl-formamide at 70℃; for 0.5h; Inert atmosphere; Stage #2: 4-fluoro-2-(trifluoromethyl)benzonitrile In N,N-dimethyl-formamide at 70℃; for 2h;	85%

L-isoserine (565-71-9, 632-11-1, 632-12-2, 632-13-3) + 4-fluoro-2-(trifluoromethyl)benzonitrile (194853-86-6) → (S)-3-((4-cyano-3-(trifluoromethyl)phenyl)amino)-2-hydroxypropanoic acid

Conditions	Yield
With triethylamine In water; dimethyl sulfoxide at 120℃; for 16h;	95%

(S)-3-Amino-1,2-propanediol (61278-21-5) + 4-fluoro-2-(trifluoromethyl)benzonitrile (194853-86-6) → (S)-4-((2,3-dihydroxypropyl)amino)-2-(trifluoromethyl)benzonitrile

Conditions	Yield
With triethylamine In dimethyl sulfoxide at 120℃; for 16h;	90%

3-Iodophenol (626-02-8) + 4-fluoro-2-(trifluoromethyl)benzonitrile (194853-86-6) → C14H7F3INO

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide at 110℃; for 2h;	86.1%

(2R,5S)-2,5-dimethyl-1-piperazinecarboxylic acid 1,1-dimethylethyl ester (309915-46-6) + 4-fluoro-2-(trifluoromethyl)benzonitrile (194853-86-6) → tert-butyl (2R,5S)-4-(4-cyano-3-(trifluoromethyl)phenyl)-2,5-dimethylpiperazine-1-carboxylate (648423-57-8)

Conditions	Yield
With potassium carbonate In water; dimethyl sulfoxide at 80℃;	90%

Methacrylamide (79-39-0) + 4-fluoro-2-(trifluoromethyl)benzonitrile (194853-86-6) → N-[4-cyano-3-(trifluoromethyl)phenyl]-2-methylacrylamide (90357-53-2)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide at 20℃; for 4h;	97%
With hydrogenchloride In hexane; water; N,N-dimethyl-formamide	97%
With sodium hydride In N,N-dimethyl-formamide at 20℃; for 3h; Inert atmosphere;	49%

(3,3,3-trifluoropropyl)amine hydrochloride (2968-33-4) + 4-fluoro-2-(trifluoromethyl)benzonitrile (194853-86-6) → 2-(trifluoromethyl)-4-[(3,3,3-trifluoropropyl)amino]benzonitrile

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide at 200℃; for 0.333333h; microwave;	61%
With N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide at 200℃; for 0.333333h;	61%

4-fluoro-2-(trifluoromethyl)benzonitrile (194853-86-6) → (1S,4S)-4-(4-hydroxy-1-methyl-pentyloxy)-2-trifluoromethyl-benzonitrile (862582-50-1) + (1S,4S)-4-(4-hydroxy-1-methylpentyloxy)-2-trifluoromethyl-benzonitrile (868597-38-0)

Conditions	Yield
Stage #1: (2S,5S)-2,5-hexanediol With sodium hydride In tetrahydrofuran for 1.08333h; Stage #2: 4-fluoro-2-(trifluoromethyl)benzonitrile In tetrahydrofuran at 20℃; for 4.58333h; Heating / reflux;	A 65% B n/a
Stage #1: (2S,5S)-2,5-hexanediol With sodium hydride In tetrahydrofuran at 6.5℃; for 1.08333h; Stage #2: 4-fluoro-2-(trifluoromethyl)benzonitrile In tetrahydrofuran at 6.5 - 20℃;	A 34% B n/a

4-fluoro-2-(trifluoromethyl)benzonitrile (194853-86-6) + trans-4-aminocyclohexan-1-ol (27489-62-9) → 4-(trans-4-hydroxy-cyclohexylamino)-2-trifluoromethyl-benzonitrile

Conditions	Yield
With potassium carbonate In water; acetonitrile at 80℃; for 72h;	80%

(2R)-2-aminopentan-1-ol (80696-30-6) + 4-fluoro-2-(trifluoromethyl)benzonitrile (194853-86-6) → (R)-4-(1-hydroxymethyl-butylamino)-2-trifluoromethyl-benzonitrile

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide at 180℃; for 0.25h; Microwave irradiation;	68%

(1S)-1-(benzylthiomethyl)-2-hydroxyethylamine (85803-43-6) + 4-fluoro-2-(trifluoromethyl)benzonitrile (194853-86-6) → 4-((R)-1-benzylsulfanylmethyl-2-hydroxy-ethylamino)-2-trifluoromethyl-benzonitrile

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide at 180℃; for 0.25h; Microwave irradiation;	71%

4-(2-hydroxy-ethyl)-piperidin-4-ol (89855-48-1) + 4-fluoro-2-(trifluoromethyl)benzonitrile (194853-86-6) → 4-[4-Hydroxy-4-(2-hydroxy-ethyl)-piperidin-1-yl]-2-trifluoromethyl-benzonitrile

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 80℃; for 4h;	68%

(R)-[1-(naphthalen-2-yl)ethyl]amine (1201-74-7, 3082-62-0, 3906-16-9, 64234-21-5) + 4-fluoro-2-(trifluoromethyl)benzonitrile (194853-86-6) → 4-{[(1R)-1-(2-Naphthyl)ethyl]amino}-2-(trifluoromethyl)benzonitrile (916810-38-3)

Conditions	Yield
With caesium carbonate In dimethyl sulfoxide at 90℃; for 2h;	74%

4-fluoro-2-(trifluoromethyl)benzonitrile (194853-86-6) → (4-fluoro-2-(trifluoromethyl)phenyl)methanamine (202522-22-3)

Conditions	Yield
With hydrogen; Raney Ni In ethanol under 2585.81 Torr;
With hydrogen In ethanol under 2585.81 Torr;	0.4 g

1-(tert-butoxycarbonyl)-4-aminopiperidine (87120-72-7) + 4-fluoro-2-(trifluoromethyl)benzonitrile (194853-86-6) → tert-butyl 4-[[4-cyano-3-(trifluoromethyl)phenyl]amino]piperidine-1-carboxylate (1247030-47-2)

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide at 100℃;	51%
With potassium carbonate In dimethyl sulfoxide at 100℃; Solvent;	51%

1,1-dimethylethylenediamine (811-93-8) + 4-fluoro-2-(trifluoromethyl)benzonitrile (194853-86-6) → 4-((2-amino-2-methylpropyl)amino)-2-(trifluoromethyl)benzonitrile

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 3h;	72%

Upstream product

• 1194-02-1 4-fluorobenzonitrile 
• 76-05-1 trifluoroacetic acid 
• 16495-77-5 [(4-chlorophenyl)thio]pentafluorobenzene 

Downstream Products

• 143782-20-1 4-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-2-(trifluoromethyl)benzonitrile 
• 405907-55-3 ethyl 1-[4-cyano-3-(trifluoromethyl)phenyl]piperidine-4-carboxylate 
• 875414-13-4 4-(3-methyl-pyrazol-1-yl)-2-trifluoromethyl-benzonitrile 
• 507239-34-1 4-(2-methyl-4-pyrrolidin-1-yl-quinolin-7-ylmethoxy)-2-trifluoromethyl-benzonitrile 
• 507241-25-0 4-(2,6-Dimethyl-4-pyrrolidin-1-yl-quinolin-7-ylmethoxy)-2-trifluoromethyl-benzonitrile 
• 507243-61-0 4-(6-Methyl-4-pyrrolidin-1-yl-quinolin-7-ylmethoxy)-2-trifluoromethyl-benzonitrile 
• 732981-34-9 (S)-4-[4-(3-Ethoxy-pyrrolidin-1-yl)-6-methyl-quinolin-7-ylmethoxy]-2-trifluoromethyl-benzonitrile 
• 1015231-54-5 C₂₆H₁₄F₆N₄O₃ 
• 925416-28-0 4-[1-(2-Chloro-phenyl)-ethoxy]-2-trifluoromethyl-benzonitrile 
• 925416-35-9 (+/-)-4-[1-(4-cyano-3-trifluoromethyl-phenoxy)-ethyl]-benzoic acid methyl ester 
• 916810-38-3 4-{[(1R)-1-(2-Naphthyl)ethyl]amino}-2-(trifluoromethyl)benzonitrile 
• 1099659-85-4 C₁₆H₁₂F₃NO 
• 876760-08-6 4-(2-ethoxy-phenoxy)-2-trifluoromethyl-benzonitrile 
• 1097081-94-1 C₁₅H₁₀F₃NO₂ 

Relevant articles and documents

Rhodium-catalyzed transformation of heteroaryl aryl ethers into heteroaryl fluorides

A rhodium complex catalyzed the conversion of the C-O bond of heteroaryl aryl ethers to the C-F bond. The reaction of (4-chlorophenylthio)pentafluorobenzene with heteroaryl aryl ethers provided heteroaryl fluorides and heteroaryl (4-chlorophenylthio)tetrafluorophenyl ethers; this involved the cleavage of a single heteroaryl C-O bond under equilibrium conditions. The reaction of heteroaryl aryl ethers with 2-fluorobenzothiazole in which two heteroaryl and aryl C-O bonds were cleaved provided heteroaryl fluorides and aryl fluorides. The reactions were applicable to five-membered and six-membered heteroaryl aryl ethers and also to diaryl ethers possessing one or two electron-withdrawing groups.