328-93-8

Basic information

• Product Name: 2,5-Bis(trifluoromethyl)aniline
• Synonyms: ALPHA,ALPHA,ALPHA,ALPHA',ALPHA',ALPHA'-HEXAFLUORO-2,5-XYLIDINE;2,5-DI(TRIFLUOROMETHYL)ANILINE;2,5-BIS(TRIFLUOROMETHYL)ANILINE;TIMTEC-BB SBB000691;2,5-BIS(TRIFLUOROMETHYL)AMILINE;2,5-Bis(trifluoromethyl)aniline 98%;2,5-Bis(trifluoromethyl)aniline98%;2,5-DIS(TRIFLUOROMETHYL)ANILINE
• CAS NO: 328-93-8
• Molecular Formula: C₈H₅F₆N
• Molecular Weight: 229.12
• EINECS: 206-490-4
• Product Categories: Fluorobenzene;Anilines, Aromatic Amines and Nitro Compounds;Nitrogen Compounds;Amines;C8;Aniline series
• Mol File: 328-93-8.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 70-71 °C15 mm Hg(lit.)
• Flash Point: 160 °F
• Appearance: Colorless or pale yellow liquid
• Density: 1.467 g/mL at 25 °C(lit.)
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: n20/D 1.432(lit.)
• Storage Temp.: Keep in dark place,Inert atmosphere,Room temperature
• Solubility: Chloroform (Slightly), Ethyl Acetate (Slightly)
• PKA: 0.24±0.10(Predicted)
• BRN: 2653046
• CAS DataBase Reference: 2,5-Bis(trifluoromethyl)aniline(CAS DataBase Reference)
• NIST Chemistry Reference: 2,5-Bis(trifluoromethyl)aniline(328-93-8)
• EPA Substance Registry System: 2,5-Bis(trifluoromethyl)aniline(328-93-8)

Safety Data

• Hazard Codes: Xn,T,Xi
• Statements: 20/21/22-36/37/38
• Safety Statements: 26-36/37/39-45-36
• RIDADR: 2810
• WGK Germany: 3
• HazardClass: 6.1
• PackingGroup: III
• Hazardous Substances Data: 328-93-8(Hazardous Substances Data)

Usage

Chemical Properties

Clear colorless liquid

Uses

Different sources of media describe the Uses of 328-93-8 differently. You can refer to the following data:
1. 2,5-Bis(trifluoromethyl)aniline is a haloalkul substituted aniline used in the preparation of anti-benign prostatic hyperplasia drug, Dutasteride (D735000).
2. 2,5-Bis(trifluoromethyl)aniline may be used in chemical synthesis.

InChI:InChI=1/C6H5BClFO2/c8-5-1-4(7(10)11)2-6(9)3-5/h1-3,10-11H

Synthetic route

1,4-Bis(trifluoromethyl)-2-nitro-benzene (320-88-7) → 2,5-bis(trifluoromethyl)aniline (328-93-8)

Conditions	Yield
With hydrogen; nickel In isopropyl alcohol at 70 - 90℃; under 3677.86 Torr; for 8h;	73%
With hydrogenchloride; tin(ll) chloride
Stage #1: 1,4-Bis(trifluoromethyl)-2-nitro-benzene With hydrogenchloride; tin(II) chloride dihdyrate In methanol; water at 20 - 50℃; Stage #2: With sodium hydroxide In water pH=10;

1,4-bis(trifluoromethyl)benzene (433-19-2) → 2,5-bis(trifluoromethyl)aniline (328-93-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: disulfuric acid; sulfuric acid; nitric acid 2: SnCl2+2H2O; concentrated HCl View Scheme
Multi-step reaction with 2 steps 1.1: nitric acid; sulfuric acid / 0 - 110 °C 2.1: hydrogenchloride; tin(II) chloride dihdyrate / water; methanol / 20 - 50 °C 2.2: pH 10 View Scheme
durch Nitrierung und Reduktion;

2-chloro 1,4-bis(trifluoromethyl)benzene (328-91-6) → 2,5-bis(trifluoromethyl)aniline (328-93-8)

Conditions	Yield
With ammonia; water at 200℃;

2-chloro-1,4-bis-(trichloromethyl)-benzene (10388-10-0) → 2,5-bis(trifluoromethyl)aniline (328-93-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: SbCl5; HF / 70 - 80 °C 2: water; ammonia / 200 °C View Scheme

N-[3-(trifluoromethyl)phenyl]-2-pyridinecarboxamide (61350-01-4) → 2,5-bis(trifluoromethyl)aniline (328-93-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: copper(I) bromide; dipotassium peroxodisulfate / acetonitrile / 12 h / 50 °C 2: hydrogenchloride / ethanol / 12 h / 100 °C View Scheme

C14H8F6N2O → 2,5-bis(trifluoromethyl)aniline (328-93-8)

Conditions	Yield
With hydrogenchloride In ethanol at 100℃; for 12h;

2,5-bis(trifluoromethyl)aniline (328-93-8) + salicylaldehyde (90-02-8) → (E)-2-(((2,5-bis(trifluoromethyl)phenyl)imino)methyl)phenol

Conditions	Yield
With formic acid In ethanol for 6h; Reflux;	96%

2,5-bis(trifluoromethyl)aniline (328-93-8) + (S)-3-keto-4-aza-5α-androstane-1-ene-17β-formyl chloride → (5α,17β)-N-(2,5-bis(trifluoromethyl)phenyl)-3-oxo-4-azaandrost-1-ene-17-carboxamide

Conditions	Yield
With pyridine In toluene at 90℃; for 3h; Temperature;	95.2%

2,5-bis(trifluoromethyl)aniline (328-93-8) + 3-oxo-4-aza-5α-androstane-17β-carboxylic acid methyl ester (73671-92-8) → (5α,17β)-N-[2,5-bis(trifluoromethyl)-phenyl]-3-oxo-4-aza-5-androstane-17-carboxamide (164656-22-8)

Conditions	Yield
Stage #1: 3-oxo-4-aza-5α-androstane-17β-carboxylic acid methyl ester With boron tribromide In dichloromethane at 25℃; for 0.333333h; Stage #2: 2,5-bis(trifluoromethyl)aniline In dichloromethane at 50℃;	93%

2,5-bis(trifluoromethyl)aniline (328-93-8) + androst-4-en-3-one-17β-carboxylic acid (302-97-6) → N-(2',5'-Bistrifluoromethylphenyl)-3-oxo-androst-4-ene-17β-carboxamide (164656-19-3)

Conditions	Yield
Stage #1: 2,5-bis(trifluoromethyl)aniline With methylmagnesium chloride In tetrahydrofuran; toluene at 20℃; Large scale; Stage #2: androst-4-en-3-one-17β-carboxylic acid With dmap; thionyl chloride; potassium carbonate In toluene at 20 - 30℃; for 3h; Large scale; Stage #3: In tetrahydrofuran; toluene at 50 - 55℃; for 8h; Large scale;	90.14%

3-allyl-2-methylthio-6-trifluoromethyl-4(3H)-pyrimidinone (216016-30-7) + 2,5-bis(trifluoromethyl)aniline (328-93-8) → 3-allyl-2-{2,5-bis(trifluoromethyl)phenyl}amino-6-trifluoromethyl-4(3H)pyrimidinone (216240-50-5)

Conditions	Yield
With ammonium chloride In N,N-dimethyl-formamide	89%

2,5-bis(trifluoromethyl)aniline (328-93-8) + 3-Oxo-4-aza-5α-androst-1-ene-17β-carboxylic acid (104239-97-6) → dutasteride

Conditions	Yield
Stage #1: 2,5-bis(trifluoromethyl)aniline With 1,8-diazabicyclo[5.4.0]undec-7-ene; 1,1'-carbonyldiimidazole In N,N-dimethyl-formamide at 105 - 110℃; Stage #2: 3-Oxo-4-aza-5α-androst-1-ene-17β-carboxylic acid In N,N-dimethyl-formamide	88.21%
Stage #1: 3-Oxo-4-aza-5α-androst-1-ene-17β-carboxylic acid With pyridine; thionyl chloride In toluene at 0 - 18℃; for 4.66667h; Stage #2: 2,5-bis(trifluoromethyl)aniline In toluene at 110℃; for 20h;
Stage #1: 3-Oxo-4-aza-5α-androst-1-ene-17β-carboxylic acid With pyridine; thionyl chloride In toluene at 0 - 18℃; for 5.6h; Stage #2: 2,5-bis(trifluoromethyl)aniline; dmap In toluene at 110℃; for 20h; Product distribution / selectivity;

2,5-bis(trifluoromethyl)aniline (328-93-8) + acetophenone (98-86-2) → (2,5-Bis-trifluoromethyl-phenyl)-[1-phenyl-eth-(E)-ylidene]-amine

Conditions	Yield
	85%

2-furyl(phenyl)methanol (60907-91-7, 113565-51-8, 132435-41-7, 4484-57-5) + 2,5-bis(trifluoromethyl)aniline (328-93-8) → (4R,5S)-4-((2,5-bis(trifluoromethyl)phenyl)amino)-5-phenylcyclopent-2-enone

Conditions	Yield
Stage #1: 2,5-bis(trifluoromethyl)aniline With (S)-6,6’-bis(1-pyranyl)-1,1'-spirobiindane-7,7’-diyl hydrogenphosphate In 1,2-dichloro-ethane at 0℃; for 0.5h; Stage #2: 2-furyl(phenyl)methanol In 1,2-dichloro-ethane at 20℃; for 22h;	83%

2,5-bis(trifluoromethyl)aniline (328-93-8) + C23H33NO4 → dutasteride

Conditions	Yield
In tetrahydrofuran for 3h;	82.2%

2,5-bis(trifluoromethyl)aniline (328-93-8) + C23H33NO4 → dutasteride

Conditions	Yield
In dichloromethane at 20℃; for 3h;	81.9%

2,5-bis(trifluoromethyl)aniline (328-93-8) + C21H29NO4 → dutasteride

Conditions	Yield
In 1,4-dioxane at 20℃; for 6h;	81.2%

2,5-bis(trifluoromethyl)aniline (328-93-8) + C22H31NO4 → dutasteride

Conditions	Yield
With pyridine at 20℃; for 3h;	80.5%

(5α,17β)-3-oxo-4-aza-5-androstane-17-(ethoxycarbonyl)-carboxylate (1416955-19-5) + 2,5-bis(trifluoromethyl)aniline (328-93-8) → (5α,17β)-N-[2,5-bis(trifluoromethyl)-phenyl]-3-oxo-4-aza-5-androstane-17-carboxamide (164656-22-8)

Conditions	Yield
With boron trifluoride diethyl etherate In acetonitrile at -10 - -8℃; for 4h;	80%

2,5-bis(trifluoromethyl)aniline (328-93-8) + methyl 3-oxo-4-aza-5α-androst-1-ene-17β-carboxylate (103335-41-7) → dutasteride

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In 2-methyltetrahydrofuran at 80℃; for 12h;	78.23%

formaldehyd (50-00-0) + 5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1,3,4-oxadiazole-2(3H)-thione + 2,5-bis(trifluoromethyl)aniline (328-93-8) → 3-(((2,5-bis(trifluoromethyl)phenyl)amino)methyl)-5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1,3,4-oxadiazole-2(3H)-thione

Conditions	Yield
In ethanol at 20℃; for 3h;	77%

2,5-bis(trifluoromethyl)aniline (328-93-8) + 1-(2-fluoro-4-methoxyphenyl)-1-ethanone (74457-86-6) → N-[2-(dimethylamino)ethyl]-7-trifluoromethyl-2-[(2-fluoro-4-methoxy)phenyl]quinolin-4-amine

Conditions	Yield
2,5-bis(trifluoromethyl)aniline; 1-(2-fluoro-4-methoxyphenyl)-1-ethanone With toluene-4-sulfonic acid In xylene Heating; Further stages.;	75%

2,5-bis(trifluoromethyl)aniline (328-93-8) + cyanoacetic acid (372-09-8) → N-[2,5-bis(trifluoromethyl)phenyl]cyanoacetamide (1140412-67-4)

Conditions	Yield
With diisopropyl-carbodiimide In N,N-dimethyl-formamide at 0 - 20℃; for 48h; Inert atmosphere;	75%
Stage #1: 2,5-bis(trifluoromethyl)aniline; cyanoacetic acid In tetrahydrofuran at 0℃; Inert atmosphere; Stage #2: With diisopropyl-carbodiimide In tetrahydrofuran at 20℃; for 24h; Inert atmosphere;

2,5-bis(trifluoromethyl)aniline (328-93-8) + 1-(4-fluorophenyl)ethanone (403-42-9) → N-[2-(dimethylamino)ethyl]-7-trifluoromethyl-2-[(4-fluoro)phenyl]quinolin-4-amine

Conditions	Yield
2,5-bis(trifluoromethyl)aniline; 1-(4-fluorophenyl)ethanone With toluene-4-sulfonic acid In xylene Heating; Further stages.;	74%

2,5-bis(trifluoromethyl)aniline (328-93-8) → 1-azido-2,5-bis(trifluoromethyl)benzene

Conditions	Yield
Stage #1: 2,5-bis(trifluoromethyl)aniline With hydrogenchloride In water for 0.0833333h; Stage #2: With sodium nitrite In water at 0℃; for 2h; Stage #3: With sodium azide In water at 0 - 20℃; for 2h;	74%

(5α,17β)-3-oxo-4-azaandrost-1-ene-17-(ethoxycarbonyl)carboxylate (1416955-22-0) + 2,5-bis(trifluoromethyl)aniline (328-93-8) → dutasteride

Conditions	Yield
With boron trifluoride diethyl etherate In acetonitrile at -15 - -8℃; for 4h;	73.8%

4-fluorobenzonitrile (1194-02-1) + 2,5-bis(trifluoromethyl)aniline (328-93-8) → 4,4'-(2,5-bis(trifluoromethyl)phenylazanediyl)dibenzonitrile

Conditions	Yield
With cesium fluoride In N,N-dimethyl-formamide at 165℃;	73%

2'-Fluoroacetophenone (445-27-2) + 2,5-bis(trifluoromethyl)aniline (328-93-8) → N-<1-(2-fluorophenyl)ethylidene>-2,5-bis(trifluoromethyl)aniline (147218-04-0)

Conditions	Yield
With toluene-4-sulfonic acid In toluene for 15h; Heating;	70%

1-(4-trifluoromethylphenyl)ethanone (709-63-7) + 2,5-bis(trifluoromethyl)aniline (328-93-8) → 2,5-bis(trifluoromethyl)-N-<1-<4-(trifluoromethyl)phenyl>ethylidene>aniline (147218-05-1)

Conditions	Yield
With toluene-4-sulfonic acid In toluene for 15h; Heating;	69%

2,5-bis(trifluoromethyl)aniline (328-93-8) + 1-(3-fluorophenyl)ethanone (455-36-7) → N-[2-(dimethylamino)ethyl]-7-trifluoromethyl-2-[(3-fluoro)phenyl]quinolin-4-amine

Conditions	Yield
2,5-bis(trifluoromethyl)aniline; 1-(3-fluorophenyl)ethanone With toluene-4-sulfonic acid In xylene Heating; Further stages.;	66%

1,1-Diphenylmethanol (91-01-0) + 2,5-bis(trifluoromethyl)aniline (328-93-8) → N-benzhydryl-2,5-bis(trifluoromethyl)aniline

Conditions	Yield
With C15H25Cl2N3NiO3; potassium tert-butylate In octane at 140℃; for 12h; Schlenk technique;	57%

2,5-bis(trifluoromethyl)aniline (328-93-8) + 3-oxo-4-aza-5α-androstane-17β-carboxylic acid (103335-55-3) → (5α,17β)-N-[2,5-bis(trifluoromethyl)-phenyl]-3-oxo-4-aza-5-androstane-17-carboxamide (164656-22-8)

Conditions	Yield
Stage #1: 3-oxo-4-aza-5α-androstane-17β-carboxylic acid With pyridine; thionyl chloride In toluene at 2 - 20℃; for 2.5h; Stage #2: 2,5-bis(trifluoromethyl)aniline In toluene at 20℃; for 192h;	56%

2-methylthio-3-propyl-6-trifluoromethyl-4(3H)-pyrimidinone (216240-56-1) + 2,5-bis(trifluoromethyl)aniline (328-93-8) → 2-{2,5-bis(trifluoromethyl)phenyl}amino-3-propyl-6-trifluoromethyl-4(3H)-pyrimidinone (216240-34-5)

Conditions	Yield
In N,N-dimethyl-formamide	54.5%

NH-pyrazole (288-13-1) + 2,5-bis(trifluoromethyl)aniline (328-93-8) → 2-(tri(1H-pyrazol-1-yl)methyl)-5-(trifluoromethyl)aniline

Conditions	Yield
With potassium hydroxide In dimethyl sulfoxide for 1h; Reflux;	53%

2,5-bis(trifluoromethyl)aniline (328-93-8) + 6-Hydroxy-2-naphthoic acid (16712-64-4) → N-[2,5-bis(trifluoromethyl)phenyl]-6-hydroxynaphthalene-2-carboxamide

Conditions	Yield
With phosphorus trichloride In chlorobenzene at 130℃; for 0.666667h; Microwave irradiation;	49%

Upstream product

• 433-19-2 1,4-bis(trifluoromethyl)benzene 
• 61350-01-4 N-[3-(trifluoromethyl)phenyl]-2-pyridinecarboxamide 
• 10388-10-0 2-chloro-1,4-bis-(trichloromethyl)-benzene 
• 320-88-7 1,4-Bis(trifluoromethyl)-2-nitro-benzene 
• 328-91-6 2-chloro 1,4-bis(trifluoromethyl)benzene 

Downstream Products

• 216240-31-2 2-{2,5-bis(trifluoromethyl)phenyl}amino-3-ethyl-6-trifluoromethyl-4(3H)-pyrimidinone 
• 216240-50-5 3-allyl-2-{2,5-bis(trifluoromethyl)phenyl}amino-6-trifluoromethyl-4(3H)pyrimidinone 
• 216240-40-3 2-{2,5-bis(trifluoromethyl)phenyl}amino-3-isobutyl-6-trifluoromethyl-4(3H)-pyrimidinone 
• 216240-30-1 2-{2,5-bis(trifluoromethyl)phenyl}amino-3-methyl-6-trifluoromethyl-4(3H)-pyrimidinone 
• 216240-34-5 2-{2,5-bis(trifluoromethyl)phenyl}amino-3-propyl-6-trifluoromethyl-4(3H)-pyrimidinone 
• 691887-53-3 N-(2,5-Bis-Trifluoromethyl-Phenyl)-3-Bromo-5-Tert-Butyl-6-Hydroxy-2-Methyl-Benzamide 
• 925234-69-1 N-[2,5-di(trifluoromethyl)phenyl]-2-oxocyclohexylsulfonamide 
• 51012-27-2 2,5-bis(trifluoromethyl)benzonitrile 
• 1445996-42-8 3-{4-[(2,5-bis(trifluoromethyl)phenylaminooxalyl)amino]phenyl}hex-4-ynoic acid 
• 164656-19-3 N-(2',5'-Bistrifluoromethylphenyl)-3-oxo-androst-4-ene-17β-carboxamide 
• 42354-31-4 2-isocyanato-1,4-bis(trifluoromethyl)benzene 
• 1796930-46-5 dutasteride 
• 164656-22-8 (5α,17β)-N-[2,5-bis(trifluoromethyl)-phenyl]-3-oxo-4-aza-5-androstane-17-carboxamide 
• 1796930-46-5 (5α,17β)-N-(2,5-bis(trifluoromethyl)phenyl)-3-oxo-4-azaandrost-1-ene-17-carboxamide 

Relevant articles and documents

Coordinating Activation Strategy-Induced Selective C?H Trifluoromethylation of Anilines

A simple protocol for the synthesis of 2-(trifluoromethyl)aniline derivatives through a coordinating activation strategy was developed. The reaction showed good reactivity and gave the target products in moderate to good yields. Pleasingly, the directing group could be recovered in excellent yield. Furthermore, this strategy allowed efficient access to the synthesis of floctafenine. A single-electron-transfer mechanism was proposed to be responsible for this trifluoromethylation reaction.

PROCESS FOR PRODUCING 2,5-BIS(TRIFLUOROMETHYL)NITROBENZENE

A process to produce 2,5-bis(trifluoromethyl)nitrobenzene in a high yield from an industrially easily available material by using a substance with which the reaction operation is simple and handling is easy, with a small number of steps under moderate reaction conditions, is provided. 1,4-bis(trifluoromethyl)benzene is nitrated by means of nitric acid in a solvent comprising as an essential component an acid selected from sulfuric acid having a sulfuric acid concentration of from 91 to 100 mass% and fuming sulfuric acid having a sulfur trioxide concentration of higher than 0 mass% and at most 20 mass%.