455-18-5

Basic information

• Product Name: Trifluoro-p-tolunitrile
• Synonyms: PTF-CN;P-TRIFLUOROMETHYLBENZONITRILE;PARA-TRIFLUOROMETHYL-BENZONITRILE;trifluoro-p-tolunitrile;ALPHA,ALPHA,ALPHA-TRIFLUORO-P-TOLUNITRILE;4-CYANOBENZOTRIFLUORIDE;4-(TRIFLUOROMETHYL)BENZONITRILE;4-(trifluoromethyl)-benzonitril
• CAS NO: 455-18-5
• Molecular Formula: C₈H₄F₃N
• Molecular Weight: 171.12
• EINECS: 207-239-1
• Product Categories: Drug Intermediates;Aromatic Nitriles;Nitrile;Fluorine Compounds;Nitriles;Benzotrifluoride Series;cyanide
• Mol File: 455-18-5.mol
• Article Data: 244

Chemical Properties

• Melting Point: 39-41 °C(lit.)
• Boiling Point: 80-81 °C20 mm Hg(lit.)
• Flash Point: 161 °F
• Appearance: white to light yellow crystal powder
• Density: 1.278 g/mL at 25 °C(lit.)
• Vapor Pressure: 0.228mmHg at 25°C
• Refractive Index: n20/D 1.4583(lit.)
• Storage Temp.: Store below +30°C.
• Water Solubility: Insoluble in water
• Sensitive: Lachrymatory
• BRN: 2046478
• CAS DataBase Reference: Trifluoro-p-tolunitrile(CAS DataBase Reference)
• NIST Chemistry Reference: Trifluoro-p-tolunitrile(455-18-5)
• EPA Substance Registry System: Trifluoro-p-tolunitrile(455-18-5)

Safety Data

• Hazard Codes: Xn,F
• Statements: 20/21/22-11
• Safety Statements: 36/37-45-36
• RIDADR: UN 1325 4.1/PG 2
• WGK Germany: 3
• TSCA: T
• HazardClass: 6.1
• PackingGroup: III
• Hazardous Substances Data: 455-18-5(Hazardous Substances Data)

Usage

Chemical Properties

white to light yellow crystal powder

General Description

4-(Trifluoromethyl)benzonitrile is a key intermediate in the synthesis of fluvoxamine. It participates in nickel-catalyzed arylcyanation reaction of 4-octyne.

InChI:InChI=1/C8H4F3N/c1-4-6(9)2-5(3-12)8(11)7(4)10/h2H,1H3

Synthetic route

4-Trifluoromethylbenzaldehyde (455-19-6) → 4-CF3C6H4CN (455-18-5)

Conditions	Yield
With trifluorormethanesulfonic acid; O-benzenesulfonyl-acetohydroxamic acid ethyl ester In dichloromethane at 23℃; for 24h; Inert atmosphere;	99%
With trifluorormethanesulfonic acid; trimethylsilylazide In acetonitrile at 25℃; for 0.00277778h; Schmidt Reaction; Flow reactor;	95%
With hydroxylamine hydrochloride In methanol; water at 20℃; for 14h; Irradiation;	94%

4-(trifluoromethyl)benzylic alcohol (349-95-1) → 4-CF3C6H4CN (455-18-5)

Conditions	Yield
Stage #1: 4-(trifluoromethyl)benzylic alcohol With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; tert-butylhypochlorite In dichloromethane at 20℃; for 1h; Inert atmosphere; Stage #2: With ammonia; iodine In dichloromethane; water at 20℃; for 2h; Inert atmosphere;	99%
With 1,4-diaza-bicyclo[2.2.2]octane; TEMPOL; ammonia; copper(l) chloride In water; acetonitrile at 20℃; for 24h;	83%
With potassium phosphate; ammonium formate In acetonitrile at 115℃; for 16h; Sealed tube; Green chemistry;	74%

p-trifluoromethylphenyl bromide (402-43-7) + K4[Fe(CN)6] → 4-CF3C6H4CN (455-18-5)

Conditions	Yield
With sodium carbonate; palladium diacetate at 140℃; for 16h;	98%
With sodium carbonate; palladium diacetate at 120℃; for 16h;	94%
With copper(l) iodide; 1,10-Phenanthroline In N,N-dimethyl acetamide at 140℃; for 24h;	75%
With sodium carbonate; potassium iodide; N,N`-dimethylethylenediamine; copper(II) bis(tetrafluoroborate) In N,N-dimethyl acetamide at 140℃; for 16h;	73%
With palladium diacetate; sodium carbonate In N,N-dimethyl acetamide at 120℃; for 2h;	90 % Chromat.

C15H10F3NO2 → 4-CF3C6H4CN (455-18-5)

Conditions	Yield
With iron(III) chloride; 2,4-Xylenol In chloroform at 20℃; for 0.05h;	96%
With iron(III) chloride; 2,6-di-tert-butyl-4-methyl-phenol In toluene at 20℃; for 0.0833333h; Schlenk technique;	82%

+ potassium trimethoxy(trifluoromethyl)boranuide → 4-CF3C6H4CN (455-18-5)

Conditions	Yield
With copper(l) iodide; 1,10-Phenanthroline In dimethyl sulfoxide at 60℃; for 16h; Inert atmosphere;	95%

p-Trifluoromethylbenzylamine (3300-51-4) → 4-CF3C6H4CN (455-18-5)

Conditions	Yield
With dmap; copper(l) iodide; 9-azabicyclo[3.3.1]nonane N-oxyl; oxygen; 4,4'-di-tert-butyl-2,2'-bipyridine In acetonitrile at 20℃; under 760.051 Torr; for 15h; Reagent/catalyst;	92%
With pyridine; 4-acetylamino-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate In dichloromethane at 20℃; for 12h; Inert atmosphere;	89%
With pyridine; Oxone; 4-acetylamino-2,2,6,6-tetramethyl-1-piperidinoxy; Pyridine hydrobromide In dichloromethane at 20℃; for 12h; Green chemistry;	86%

p-trifluoromethylphenyl bromide (402-43-7) + dicyanozinc (557-21-1) → 4-CF3C6H4CN (455-18-5)

Conditions	Yield
With triphenylphosphine; zinc; palladium on activated charcoal In N,N-dimethyl acetamide for 20h; Heating;	91%
With 1,1'-bis-(diphenylphosphino)ferrocene; polymethylhydrosiloxane; palladium diacetate In water at 80℃; for 1.5h;	61%

zinc cyanide + 4-chlorobenzotrifluoride (98-56-6) → 4-CF3C6H4CN (455-18-5)

Conditions	Yield
With racemic-2-(di-tert-butylphosphino)-1,1′-binaphthyl; palladium diacetate; zinc In N,N-dimethyl-formamide at 110℃; for 1h; Inert atmosphere;	91%

(trifluoromethyl)trimethylsilane (81290-20-2) + 4-Aminobenzonitrile (873-74-5) → 4-CF3C6H4CN (455-18-5)

Conditions	Yield
Stage #1: 4-Aminobenzonitrile With tert.-butylnitrite; toluene-4-sulfonic acid In acetonitrile at 20℃; for 0.5h; Sandmeyer Reaction; Inert atmosphere; Stage #2: (trifluoromethyl)trimethylsilane With copper(I) thiocyanate; caesium carbonate In acetonitrile at 20℃; for 0.202833h; Sandmeyer Reaction; Inert atmosphere;	91%

4-iodobenzonitrile (3058-39-7) + Cu(2+)*2C2F3O4S(1-) → 4-CF3C6H4CN (455-18-5)

Conditions	Yield
With copper In N,N-dimethyl-formamide at 20℃; for 3h; Inert atmosphere;	90%

4-trifluoromethylphenylboronic acid (128796-39-4) + ethyl (ethoxymethylene)cyanoacetate (94-05-3) → 4-CF3C6H4CN (455-18-5)

Conditions	Yield
With tert.-butylhydroperoxide; copper(l) iodide In N,N-dimethyl-formamide at 130℃; for 24h;	90%

zinc(II) cyanide (557-21-1) + p-trifluoromethylphenyl bromide (402-43-7) → 4-CF3C6H4CN (455-18-5)

Conditions	Yield
With dichloro[9,9-dimethyl-4,5- bis(diphenylphosphino)xanthene]palladium (II); N-ethyl-N,N-diisopropylamine In N,N-dimethyl acetamide at 85℃; Sealed tube;	90%

4-chlorobenzotrifluoride (98-56-6) + potassium ferrocyanide → 4-CF3C6H4CN (455-18-5)

Conditions	Yield
With palladium diacetate; sodium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene In 1-methyl-pyrrolidin-2-one at 170℃; for 11h; Reagent/catalyst; Temperature; Inert atmosphere;	90%
With tetra(adamantyl)biphosphine; palladium diacetate; sodium carbonate In 1-methyl-pyrrolidin-2-one at 160℃; for 16h; Inert atmosphere;	81 %Chromat.

p-trifluoromethylphenyl bromide (402-43-7) + formamide (77287-34-4, 77287-35-5, 60100-09-6) → 4-CF3C6H4CN (455-18-5)

Conditions	Yield
With 1,3,5-trichloro-2,4,6-triazine; palladium on activated charcoal; potassium carbonate; triphenylphosphine at 25 - 130℃; for 12.1667h;	90%
With [2,2]bipyridinyl; aluminum (III) chloride; nickel(II) acetylacetonate; zinc(II) oxide In 1,2-dimethoxyethane at 145℃; for 12h;	66%

5-(4-(trifluoromethyl)phenyl)-1,3,4-oxadiazole (477886-85-4) → 4-CF3C6H4CN (455-18-5)

Conditions	Yield
With sodium t-butanolate In N,N-dimethyl-formamide at 20℃; for 8h;	89%

4-bromobenzenecarbonitrile (623-00-7) + dimesityl(trifluoromethyl)sulfonium trifluoromethanesulfonate → 4-CF3C6H4CN (455-18-5)

Conditions	Yield
With dilithium tetrabromocuprate; 1,1,1,3,3,3-hexamethyl-2-(trimethylsilyl)-2-trisilanol; Ir(2-(2,4-difluorophenyl)-5-fluoropyridine)2(4,4'-di(trifluoromethyl)-2,2'-bipyridyl)PF6; sodium carbonate In acetone at 35℃; for 8h; Catalytic behavior; Reagent/catalyst; Solvent; Irradiation;	89%

4-iodobenzonitrile (3058-39-7) + N-methyl-2-phenyl-2-trifluoromethylbenzimidazoline → 4-CF3C6H4CN (455-18-5)

Conditions	Yield
With potassium carbonate; copper(l) chloride at 60℃; for 48h; Inert atmosphere;	89%
With copper(l) iodide; 4,4'-Dimethoxy-2,2'-bipyridin; potassium carbonate In benzonitrile at 90℃; for 48h;	73 %Spectr.

4-iodobenzonitrile (3058-39-7) + N-methyl-2-(4-methoxyphenyl)-2-trifluoromethylbenzimidazoline → 4-CF3C6H4CN (455-18-5)

Conditions	Yield
With potassium carbonate; copper(l) chloride In benzonitrile at 60℃; for 48h;	88%

p-trifluoromethylphenyl bromide (402-43-7) + C4H2Cl2N4O*ClH → 4-CF3C6H4CN (455-18-5)

Conditions	Yield
With palladium on activated charcoal; potassium carbonate; triphenylphosphine at 25 - 130℃; for 12.1667h;	88%

p-trifluoromethylphenyl bromide (402-43-7) + 2-hydroxy-2-methylpropanenitrile (75-86-5) → 4-CF3C6H4CN (455-18-5)

Conditions	Yield
Stage #1: p-trifluoromethylphenyl bromide With copper(l) iodide; 1,10-Phenanthroline; potassium iodide In N,N-dimethyl-formamide at 110℃; for 6h; Stage #2: 2-hydroxy-2-methylpropanenitrile With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 110℃; for 60h;	87%
With 1-Butylimidazole; copper(l) iodide; sodium carbonate In o-xylene at 150℃; for 21h; Inert atmosphere; Pressure tube;	71%
With N,N,N,N,-tetramethylethylenediamine; 1,5-bis-(diphenylphosphino)pentane; sodium carbonate; palladium diacetate In N,N-dimethyl acetamide at 100℃; for 21h;	100 % Chromat.

4-CF3C6H4CN (455-18-5) + 4,4,5,5-tetramethyl-[1,3,2]-dioxaboralane (25015-63-8) → 4,4,5,5-tetramethyl-N-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N-(4-(trifluoromethyl)-benzyl)-1,3,2-dioxaborolan-2-amine

Conditions	Yield
With silver hexafluoroantimonate at 60℃; for 12h; Inert atmosphere; Glovebox;	99%
With manganese(II) triflate bis-acetonitrile solvate; potassium tert-butylate In benzene-d6 at 20℃; for 3h; Inert atmosphere; Glovebox;	99%
With C26H50N6Zn2 In neat (no solvent) at 60℃; Schlenk technique; Glovebox;	98%

4-CF3C6H4CN (455-18-5) + benzyl chloride (100-44-7) → N-benzyl-4-trifluoromethylbenzamide

Conditions	Yield
With iron(II) chloride tetrahydrate In neat (no solvent) at 80℃; for 1h; Ritter Amidation;	99%
With zinc perchlorate In neat (no solvent) at 80℃; for 2h; Ritter Amidation;	98%

4-CF3C6H4CN (455-18-5) → (Z)-N'-hydroxy-4-(trifluoromethyl)benzimidamide (184778-31-2, 22179-86-8, 1219624-50-6)

Conditions	Yield
With hydroxylamine hydrochloride; potassium tert-butylate In methanol; toluene at 75 - 80℃; for 17h;	98%
With hydroxylamine hydrochloride; sodium hydroxide In ethanol; water at 20℃; for 15h;	95%
With hydroxylamine hydrochloride; sodium hydroxide In ethanol; water at 20℃; for 15h;	95%

4-CF3C6H4CN (455-18-5) + dimethyl 2,2-di(but-2-yn-1-yl)malonate (107428-05-7) → dimethyl 1,4-dimethyl-3-(4-(trifluoromethyl)phenyl)-5H-cyclopenta[c]pyridine-6,6(7H)-dicarboxylate

Conditions	Yield
With bis(1,5-cyclooctadiene)nickel (0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene In toluene at 20℃; for 3h; Inert atmosphere;	98%
With bis(1,5-cyclooctadiene)nickel (0); 1,3-bis(2,6-diisopropylphenyl)dihydroimidazol-2-ylidene In toluene at 20℃; for 2h;	94%

4-CF3C6H4CN (455-18-5) → N-hydroxy-4-(trifluoromethyl)benzimidamide (22179-86-8)

Conditions	Yield
With hydroxylamine hydrochloride; sodium hydrogencarbonate In ethanol; water at 100℃; for 3h;	98%
With hydroxylamine In ethanol; water at 20℃; Reflux;	93%
With hydroxylamine hydrochloride; sodium carbonate In ethanol; water for 6h; Reflux;	92%

4-CF3C6H4CN (455-18-5) + benzo[1,3,2]dioxaborole (274-07-7) → N-(benzo[d][1,3,2]dioxaborol-2-yl)-N-(4-(trifluoromethyl)benzyl)benzo[d][1,3,2]dioxaborol-2-amine

Conditions	Yield
With C29H28Cl2N2Ti In neat (no solvent) at 65℃; for 10h; Schlenk technique; Inert atmosphere; Glovebox; chemoselective reaction;	98%
With nickel(II) bis(2,2,6,6-tetramethylheptane-3,5-dionate) In benzene at 20℃; for 18h;	85%
With [κ2-{2-F-C6H4NP(Se)Ph2}2Al(Me)] In neat (no solvent) at 60℃; for 5h; Schlenk technique; Glovebox; Inert atmosphere; chemoselective reaction;	92 %Spectr.

4-CF3C6H4CN (455-18-5) + 9-bora-bicyclo[3.3.1]nonane (280-64-8) → C16H19BF3N

Conditions	Yield
With C33H47O2PRuSi2 In tetrahydrofuran-d8 at 40℃; for 0.5h; Inert atmosphere; Schlenk technique;	98%

4-CF3C6H4CN (455-18-5) + methyl 2-diazo-2-(fluorosulfonyl)acetate → 5-methoxy-2-(4-(trifluoromethyl)phenyl)oxazole-4-sulfonyl fluoride

Conditions	Yield
Stage #1: 4-CF3C6H4CN With dirhodium tetraacetate In chloroform at 70℃; Stage #2: methyl 2-diazo-2-(fluorosulfonyl)acetate In chloroform at 70℃; for 12h;	98%

methanol (67-56-1) + 4-CF3C6H4CN (455-18-5) → 4-Trifluoromethyl-benzimidic acid methyl ester; hydrochloride (56108-08-8)

Conditions	Yield
With hydrogenchloride In diethyl ether at 0 - 5℃;	97%
With hydrogenchloride In diethyl ether at 3 - 4℃;

4-CF3C6H4CN (455-18-5) + tert-butyl alcohol (75-65-0) → N-(tert-butyl)-4-(trifluoromethyl)benzamide (91888-96-9)

Conditions	Yield
With H-form microporous zeolite Y nanoparticle assemblies at 120℃; for 12h; Ritter Amidation; Inert atmosphere;	97%
With bismuth(lll) trifluoromethanesulfonate; water In nitrobenzene Ritter reaction;	95%
With aluminum potassium sulfate dodecahydrate In neat (no solvent) at 100℃; for 2.5h; Ritter Amidation;	80%

3-tert-butyltitanacyclobutane (75687-68-2) + 4-CF3C6H4CN (455-18-5) → (C5H5)2Ti(C3H2N2)(C6H4CF3)2

Conditions	Yield
In benzene (Ar); Ti compd. in benzene was stirred with CF3C6H4CN (1:2,0 mol) at 50°C for 5,5 h; removal of solvent yielded the product;	97%

Upstream product

• 623-03-0 4-Cyanochlorobenzene 
• 75-63-8 Bromotrifluoromethane 
• 460-19-5 ethanedinitrile 
• 98-08-8 α,α,α-trifluorotoluene 
• 623-00-7 4-bromobenzenecarbonitrile 
• 100-17-4 para-methoxynitrobenzene 
• 115127-52-1 3-chloro-3-(4-trifluoromethylphenyl)diaziridine 
• 930-69-8 sodium thiophenolate 
• 75-36-5 acetyl chloride 
• 293314-17-7 C₈H₅F₃N₄O 
• 98-56-6 4-chlorobenzotrifluoride 
• 75-86-5 2-hydroxy-2-methylpropanenitrile 
• 402-43-7 p-trifluoromethylphenyl bromide 
• 557-21-1 dicyanozinc 

Downstream Products

• 455-19-6 4-Trifluoromethylbenzaldehyde 
• 56108-08-8 4-Trifluoromethyl-benzimidic acid methyl ester; hydrochloride 
• 131561-45-0 ((CH₃)3Si)2NC(C₆H₄CF₃)NP(C₆H₅)2NSi(CH₃)3 
• 131561-46-1 C₂₉H₄₁F₃N₃PSi₃ 
• 76047-28-4 β-amino-p-trifluoromethylcinnamonitrile 
• 34328-30-8 4-trifluoromethyl-4′-methylbenzophenone 
• 71682-89-8 3-amino-3-[4-(trifluoromethyl)phenyl]prop-2-enenitrile 
• 183280-22-0 (5-Fluoro-2-methoxy-phenyl)-(4-trifluoromethyl-phenyl)-methanone 
• 26771-69-7 2-methoxy-1-(4-(trifluoromethyl)phenyl)ethan-1-one 
• 628732-67-2 3,6-bis(4-trifluoromethyl-phenyl)-1,2-dihydro-1,2,4,5-tetrazine 
• 863868-28-4 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(trifluoromethyl)benzonitrile 
• 42916-66-5 1-(4-(trifluoromethyl)phenyl)pentan-1-one 
• 583030-50-6 7-(4-trifluoromethylphenyl)-2,3-dihydro-5H-[1,3]oxazolo[3,2-a]pyrimidin-5-one 
• 583030-39-1 7-(4-trifluoromethylphenyl)-2,3-dihydro-5H-[1,3]oxazolo[3,2-c]pyrimidin-5-one 

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