1535-75-7

Basic information

• Product Name: 2-(Trifluoromethoxy)aniline
• Synonyms: 2-(TrifloroMethoxy)aniline;2-(TrifluoroMethoxy)aniline, 97.5%;2-(TrifluoroMethoxy)aniline, 97+%;TrifluoroMethoxy)anilin;2-(Trifluoromethoxy)aniline,o-Aminotrifluoromethoxybenzene;2-(TRIFLUOROMETHOXY)ANILINE;2-TRIFLUOROMETHOXY-PHENYLAMINE;ALPHA,ALPHA,ALPHA-TRIFLUORO-O-ANISIDINE
• CAS NO: 1535-75-7
• Molecular Formula: C₇H₆F₃NO
• Molecular Weight: 177.12
• EINECS: 216-257-9
• Product Categories: Amines;Building Blocks;C7;Chemical Synthesis;Nitrogen Compounds;Organic Building Blocks;Halogenated Heterocycles ,Pyrimidines;Trifluoroanisole series;Trifluoromethoxybenzene Series;Anilines, Aromatic Amines and Nitro Compounds
• Mol File: 1535-75-7.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 61-63 °C (15 mmHg)
• Flash Point: 54°C
• Appearance: Clear colorless to yellow/Liquid
• Density: 1,301 g/cm3
• Vapor Pressure: 0.000695mmHg at 25°C
• Refractive Index: 1.4614-1.4634
• Storage Temp.: Keep in dark place,Inert atmosphere,Room temperature
• PKA: 2.45±0.10(Predicted)
• BRN: 2803814
• CAS DataBase Reference: 2-(Trifluoromethoxy)aniline(CAS DataBase Reference)
• NIST Chemistry Reference: 2-(Trifluoromethoxy)aniline(1535-75-7)
• EPA Substance Registry System: 2-(Trifluoromethoxy)aniline(1535-75-7)

Safety Data

• Hazard Codes: Xn,T,Xi
• Statements: 36/37/38-20/21/22-10
• Safety Statements: 36/37/39-26-45-16-36
• RIDADR: 1993
• WGK Germany: 3
• HazardClass: 3
• PackingGroup: III
• Hazardous Substances Data: 1535-75-7(Hazardous Substances Data)

Usage

Chemical Properties

CLEAR, VERY FAINTLY YELLOW LIQUID

Uses

2-(Trifluoromethoxy)aniline may be used in the preparation of 2-amino-6-(trifluoromethoxy)benzothiazole (SKA-35).

InChI:InChI=1/C13H5F5O/c14-8-7(9(15)11(17)12(18)10(8)16)13(19)6-4-2-1-3-5-6/h1-5H

Synthetic route

1-bromo-2-(trifluoromethoxy)benzene (64115-88-4) → 2-trifluoromethoxy aniline (1535-75-7)

Conditions	Yield
With ammonium hydroxide; L-2-O-methyl-chiro-inositol; copper(II) acetate monohydrate In 1-methyl-pyrrolidin-2-one at 110℃; for 12h;	82%

1-chloro-4-(trifluoromethoxy)benzene (461-81-4) → 2-trifluoromethoxy aniline (1535-75-7) + m-trifluoromethoxyaniline (1535-73-5)

Conditions	Yield
Stage #1: 1-chloro-4-(trifluoromethoxy)benzene With sulfuric acid; nitric acid at 0 - 45℃; Stage #2: With palladium on activated charcoal; hydrogen; triethylamine In methanol at 80℃; under 15001.5 Torr; Temperature; Pressure; Autoclave; Overall yield = 98 percent; Overall yield = 177.12 g;

2-trifluoromethoxy aniline (1535-75-7) + 2-(trifluoromethoxy)benzenesulfonyl chloride (103008-51-1) → 2-trifluoromethoxy-benzenesulphonic acid amide (37526-59-3)

Conditions	Yield
	99.4%

di-tert-butyl dicarbonate (24424-99-5) + 2-trifluoromethoxy aniline (1535-75-7) → tert-butyl N-[2-(trifluoromethoxy)phenyl]carbamate (561304-39-0)

Conditions	Yield
In toluene at 100℃; for 2h;	98%
In toluene Heating;	76%

2-trifluoromethoxy aniline (1535-75-7) + ethyl acetoacetate (141-97-9) → 3-oxo-2-(2-(2-(trifluoromethoxy)phenyl)hydrazono)butanoic acid ethyl ester (1620683-57-9)

Conditions	Yield
Stage #1: 2-trifluoromethoxy aniline With hydrogenchloride; sodium nitrite In water at 0℃; for 0.5h; Stage #2: ethyl acetoacetate With sodium acetate In ethanol; water at 0℃;	92.3%
Stage #1: 2-trifluoromethoxy aniline With hydrogenchloride; sodium nitrite In water at 0℃; for 0.0833333h; Stage #2: ethyl acetoacetate With ammonium acetate In ethanol; water
Stage #1: 2-trifluoromethoxy aniline With hydrogenchloride; sodium nitrite In water at 0℃; for 0.0833333h; Stage #2: ethyl acetoacetate With ammonium acetate In ethanol; water at 0℃; for 0.5h;

2-trifluoromethoxy aniline (1535-75-7) + t-butyl 2-diazopropanoate (805237-13-2) → (-)-tert-butyl 2-((2-(trifluoromethoxy)phenyl)amino)propanoate

Conditions	Yield
With C32H30N4O4; copper(l) chloride In dichloromethane at 0℃; for 18h; Inert atmosphere; Molecular sieve; optical yield given as %ee; enantioselective reaction;	92%

2-trifluoromethoxy aniline (1535-75-7) + sodium formate (141-53-7) → N-(2-(trifluoromethoxy)phenyl)formamide

Conditions	Yield
With formic acid for 12h; Reflux;	90.56%

2-trifluoromethoxy aniline (1535-75-7) + ethyl 2-chloro-3-oxo-butyrate (609-15-4) → ethyl 2-chloro-2-(2-(2-(trifluoromethoxy)phenyl)hydrazono)acetate

Conditions	Yield
Stage #1: 2-trifluoromethoxy aniline With hydrogenchloride; sodium nitrite In ethanol; water at 0 - 5℃; for 0.5h; Stage #2: ethyl 2-chloro-3-oxo-butyrate With sodium acetate In ethanol; water at 0 - 25℃;	90%

tin(II)chloride dihydrate + 2-trifluoromethoxy aniline (1535-75-7) → [2-(trifluoromethoxy)phenyl]hydrazine hydrochloride

Conditions	Yield
With sodium nitrite In hydrogenchloride; water	88%

ortho-nitrobenzoic acid (552-16-9) + 2-trifluoromethoxy aniline (1535-75-7) → 2-nitro-N-(2-(trifluoromethoxy)phenyl)benzamide (939920-68-0)

Conditions	Yield
Stage #1: ortho-nitrobenzoic acid With thionyl chloride In N,N-dimethyl-formamide; benzene Reflux; Stage #2: 2-trifluoromethoxy aniline With triethylamine In dichloromethane; N,N-dimethyl-formamide at 0 - 20℃;	88%

2-trifluoromethoxy aniline (1535-75-7) + cyanoacetic acid (372-09-8) → 2-cyano-N-(2-trifluoromethoxyphenyl)acetamide

Conditions	Yield
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 1h; Inert atmosphere;	87%

3-bromo-3-methyl-2-indolinone (2406-05-5) + 2-trifluoromethoxy aniline (1535-75-7) → (R)-3-methyl-3-((2-(trifluoromethoxy)phenyl)amino)indolin-2-one

Conditions	Yield
Stage #1: 3-bromo-3-methyl-2-indolinone With nickel(II) tetrafluoroborate hexahydrate; C42H66N4O8 In ethyl acetate at 35℃; for 0.583333h; Stage #2: With N-ethyl-N,N-diisopropylamine In ethyl acetate at 0℃; for 0.166667h; Stage #3: 2-trifluoromethoxy aniline In ethyl acetate at 0℃; for 24h; enantioselective reaction;	86%

chloral hydrate (302-17-0) + 2-trifluoromethoxy aniline (1535-75-7) → 2-hydroxyimino-N-(2-trifluoromethoxy-phenyl)-acetamide

Conditions	Yield
With hydrogenchloride; hydroxylamine hydrochloride; sodium sulfate at 55℃; Sandmeyer reaction;	85%
With hydrogenchloride; hydroxylamine hydrochloride; sodium sulfate at 55℃; Sandmeyer reaction;	85%

2-trifluoromethoxy aniline (1535-75-7) + C20H21NO4 → C27H25F3N2O4

Conditions	Yield
With dmap; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 12h;	85%

2-trifluoromethoxy aniline (1535-75-7) + C20H21NO4 → C27H25F3N2O4

Conditions	Yield
With dmap; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 12h; Inert atmosphere;	85%

2-trifluoromethoxy aniline (1535-75-7) + tetra(n-butyl)ammonium hydrogensulfate (32503-27-8) → tetrabutylammonium (2‐(trifluoromethoxy)phenyl)sulfamate

Conditions	Yield
Stage #1: 2-trifluoromethoxy aniline With chlorosulfonic acid; triethylamine In dichloromethane at 0 - 20℃; Inert atmosphere; Stage #2: With sodium hydroxide In dichloromethane; water Stage #3: tetra(n-butyl)ammonium hydrogensulfate In dichloromethane; water	85%

4-bromoohenyl methyl sulfone (3466-32-8) + 2-trifluoromethoxy aniline (1535-75-7) → N-(4-(methylsulfonyl)phenyl)-2-(trifluoromethoxy)aniline

Conditions	Yield
With 1,3-bis[(diphenylphosphino)propane]dichloronickel(II); N,N,N′,N′-tetramethyl-N″-tert-butylguanidine; 4,4'-di-tert-butyl-2,2'-bipyridine; zinc In dimethyl sulfoxide at 80℃; for 8h; Reagent/catalyst; Inert atmosphere;	85%

(4-bromo-3-methylphenyl)(morpholino)methanone (149105-06-6) + 2-trifluoromethoxy aniline (1535-75-7) → C19H19F3N2O3

Conditions	Yield
With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); C37H43N2O4P In 1,4-dioxane at 90℃; for 18h;	82%

Octanethiol (111-88-6) + 2-trifluoromethoxy aniline (1535-75-7) → 2-(n-octylthio)-1-trifluoromethoxybenzene

Conditions	Yield
With tert.-butylnitrite; C29H23N6Ru2(2+)*2Cl(1-)*6H2O; toluene-4-sulfonic acid In acetonitrile at 20℃; for 5h; Irradiation;	81%

cycl-isopropylidene malonate (2033-24-1) + 2-trifluoromethoxy aniline (1535-75-7) → C10H6F3NO3

Conditions	Yield
Stage #1: cycl-isopropylidene malonate; 2-trifluoromethoxy aniline Heating; Stage #2: With Eaton’s reagent Heating;	81%

2-trifluoromethoxy aniline (1535-75-7) + p-cyanophenyl isocyanate (40465-45-0) → 1-(4-cyanophenyl)-3-(2-trifluoromethoxyphenyl)urea (1416274-64-0)

Conditions	Yield
In tetrahydrofuran at 20℃;	80.4%

2-methylquinoline (91-63-4) + 2-trifluoromethoxy aniline (1535-75-7) → (4-amino-3-(trifluoromethoxy)phenyl)(quinolin-2-yl)methanone

Conditions	Yield
With iodine; oxygen; dimethyl sulfoxide; salicylic acid at 90℃; under 760.051 Torr; for 16h; Schlenk technique; regioselective reaction;	80%

3-Phenylpropenol (104-54-1) + 2-trifluoromethoxy aniline (1535-75-7) → 2-phenyl-8-(trifluoromethoxy)quinoline

Conditions	Yield
With oxygen; palladium diacetate In dimethyl sulfoxide at 130℃; under 760.051 Torr; for 12h;	78%

2-trifluoromethoxy aniline (1535-75-7) + 1-(2,4-dinitrophenyl)-1′-(2-isopropylphenyl)-4,4′-bipyridinium bis(tetrafluoroborate) → 1-(2-trifluoromethoxyphenyl)-1′-(2-isopropylphenyl)-4,4′-bipyridinium bis(tetrafluoroborate)

Conditions	Yield
In methanol for 48h; Reflux;	77%

N-vinyl-2-oxazolidone (4271-26-5) + 2-trifluoromethoxy aniline (1535-75-7) + Diethyl 2-bromomalonate (685-87-0) → diethyl 2-(2-(2-oxooxazolidin-3-yl)-2-((2-trifluoromethoxyphenyl)amino)ethyl)malonate

Conditions	Yield
With (4,4'-di-tert-butyl-2,2'-dipyridyl)-bis-(2-phenylpyridine(-1H))-iridium(III) hexafluorophosphate; triethylamine In acetonitrile at 20℃; for 3h; Inert atmosphere; Sealed tube; Irradiation;	77%

2-trifluoromethoxy aniline (1535-75-7) + ortho-anisaldehyde (135-02-4) → N-(2-methoxybenzyl)-2-(trifluoromethoxy)aniline

Conditions	Yield
With sodium tris(acetoxy)borohydride In dichloromethane at 20℃; for 2h;	75%

2-trifluoromethoxy aniline (1535-75-7) + acetophenone (98-86-2) → 1-(4-amino-3-(trifluoromethoxy)phenyl)-2-phenylethane-1,2-dione

Conditions	Yield
With copper(l) iodide; boron trifluoride diethyl etherate; oxygen In dimethyl sulfoxide at 105℃; for 14h; regioselective reaction;	75%

cycl-isopropylidene cyclopropane-1,1-dicarboxylate (5617-70-9) + 2-trifluoromethoxy aniline (1535-75-7) → 2-oxo-1-(2-(trifluoromethoxy)phenyl)pyrrolidine-3-carboxylic acid

Conditions	Yield
In N,N-dimethyl-formamide at 30 - 35℃; for 12h;	72.3%

(Z)-2,2'-dibromostilbene (56667-12-0, 108474-32-4, 56667-11-9) + 2-trifluoromethoxy aniline (1535-75-7) → 5-(2-(trifluoromethoxy)phenyl)-5H-dibenzo[b,f]azepine (1414856-44-2)

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; bis[2-(diphenylphosphino)phenyl] ether In toluene at 120℃; for 10h; Schlenk technique; Inert atmosphere;	72%

2-trifluoromethoxy aniline (1535-75-7) + 1,4-dinitro-1H-imidazole (19182-81-1) → 4-nitro-1-{2-(trifluoromethoxy)phenyl}-1H-imidazole (1297344-95-6)

Conditions	Yield
In methanol; water at 20℃; Darkness;	71%

Upstream product

• 461-81-4 1-chloro-4-(trifluoromethoxy)benzene 
• 64115-88-4 1-bromo-2-(trifluoromethoxy)benzene 

Downstream Products

• 103008-51-1 2-(trifluoromethoxy)benzenesulfonyl chloride 
• 133115-76-1 [2-(trifluoromethoxy)phenyl]hydrazine hydrochloride 
• 1048672-58-7 1-(2,6-dimethylphenyl)-3-(2-(trifluoromethoxy)phenyl)urea 
• 656227-27-9 2-chloro-N-(2-(trifluoromethoxy)phenyl)acetamide 
• 175205-33-1 1-isothiocyanato-2-trifluoromethoxybenzene 
• 561304-39-0 tert-butyl N-[2-(trifluoromethoxy)phenyl]carbamate 
• 175205-24-0 N-<2-(trifluoromethoxy)phenyl>thiourea 
• 186386-95-8 1-(2-trifluoromethoxyphenyl)-piperazine 
• 17128-13-1 4-Dimethylamino-2'-trifluormethoxy-azobenzol 
• 58140-27-5 C₁₆H₉F₆N₅O₂ 
• 1143579-11-6 4-(3-methoxyphenyl)-1-[2-(trifluoromethoxy)phenyl]piperidine-4-carbonitrile 

Relevant articles and documents

Co-production preparation method of o-amino trifluoromethoxy benzene and m-amino trifluoromethoxy benzene

The invention discloses a co-production preparation method of o-amino trifluoromethoxybenzene and m-amino trifluoromethoxybenzene, and belongs to the technical field of fine chemical engineering. Thepreparation method comprises the following steps: (1) nitration reaction: carrying out nitration reaction on 4-chlorine-trifluoromethoxybenzene to obtain a mixture of 4-chlorine-2-nitro- trifluoromethoxy benzene and 4-chlorine-3-nitro-trifluoromethoxybenzene; (2) reduction and dechlorination: carrying out reduction and dechlorination on the mixture of the 4-chloro-2-nitro-trifluoromethoxybenzene and the 4-chloro-3-nitro-trifluoromethoxybenzene to obtain o-amino trifluoromethoxybenzene and m-amino trifluoromethoxybenzene; and (3) rectification separation: separating the o-amino trifluoromethoxybenzene from the m-amino trifluoromethoxybenzene through rectification so as to realize co-production. The method is low in cost and high in yield, two useful chemical products are obtained at the same time, the process is simple, and industrial production is easy to achieve.

Method for preparing 2-trifluoro-methoxy-aniline

PCT No. PCT/FR98/01050 Sec. 371 Date Nov. 29, 1999 Sec. 102(e) Date Nov. 29, 1999 PCT Filed May 26, 1998 PCT Pub. No. WO98/54121 PCT Pub. Date Dec. 3, 1998This invention relates to a method for the preparation of a compound of formula I comprising the steps consisting in: a) optionally reacting a compound of general formula II: with a nitration reagent b) reducing the compound obtained in a) c) subjecting the compound obtained in b) to a dehydrochlorination in order to obtain the compound of formula I: and d) isolating the compound obtained in step c) from the reaction mixture.