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

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

Uses

Used in Pharmaceutical Industry:
4-Fluoro-2-trifluoromethylbenzonitrile is used as a pharmaceutical intermediate for the development of various drugs. Its unique chemical structure allows it to serve as a building block in the synthesis of complex molecules with potential therapeutic applications.
Used in Chemical Synthesis:
In the field of chemical synthesis, 4-Fluoro-2-trifluoromethylbenzonitrile is utilized for the synthesis of diphenylthioethers. These compounds have a wide range of applications, including their use as additives, stabilizers, and intermediates in the production of various chemicals and materials.
Overall, 4-Fluoro-2-trifluoromethylbenzonitrile is a versatile compound with significant potential in both the pharmaceutical and chemical synthesis industries. Its unique properties and applications make it an important compound for researchers and chemists working in these fields.

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

• 507241-01-2 4-(4-chloro-2-methyl-quinolin-7-ylmethoxy)-2-trifluoromethyl-benzonitrile 
• 143782-20-1 4-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-2-(trifluoromethyl)benzonitrile 
• 90357-53-2 N-[4-cyano-3-(trifluoromethyl)phenyl]-2-methylacrylamide 
• 405907-55-3 ethyl 1-[4-cyano-3-(trifluoromethyl)phenyl]piperidine-4-carboxylate 
• 262295-65-8 (+/-)-4-(3-methylpiperazin-1-yl)-2-(trifluoromethyl)benzonitrile 
• 904301-11-7 4-[(2-aminoethyl)amino]-2-(trifluoromethyl)benzonitrile 
• 262295-73-8 tert-butyl 4-[4-cyano-3-(trifluoromethyl)phenyl]-3-methylpiperazine-1-carboxylate 
• 262295-70-5 4-(4-benzyl-3-oxopiperazin-1-yl)-2-(trifluoromethyl)benzonitrile 
• 262295-71-6 (+/-)-cis-4-(3,5-dimethylpiperazin-1-yl)-2-(trifluoromethyl)benzonitrile 
• 875414-13-4 4-(3-methyl-pyrazol-1-yl)-2-trifluoromethyl-benzonitrile 
• 262295-90-9 (2S,5R)-4-(4-benzyl-2,5-dimethylpiperazin-1-yl)-2-trifluoromethylbenzonitrile 
• 1003838-32-1 C₁₂H₁₁F₃N₂ 
• 927692-46-4 C₁₄H₁₅F₃N₂ 
• 90357-06-5 Bicalutamide 

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.

Silver-Catalyzed C-H Trifluoromethylation of Arenes Using Trifluoroacetic Acid as the Trifluoromethylating Reagent

Direct trifluoromethylation of arenes using TFA as the trifluoromethylating reagent was achieved with Ag as the catalyst. This reaction not only provides a new protocol for aryl C-H trifluoromethylation, but the generation of CF3· from TFA may prove useful in other contexts and could potentially be extended to other trifluoromethylation reactions. (Chemical Equation Presented).