363-51-9

Usage

Chemical Properties

Clear pale yellow liquid

InChI:InChI=1/C6H5ClFN/c7-4-2-1-3-5(8)6(4)9/h1-3H,9H2

Synthetic route

2'-Chloro-6'-fluorobenzanilide (90493-88-2) → 2-chloro-6-fluoroaniline (363-51-9)

Conditions	Yield
With sulfuric acid for 3h; Heating;	71%

2-chloro-6-fluorobenzoic acid (434-75-3) → 2-chloro-6-fluoroaniline (363-51-9)

Conditions	Yield
With sodium azide; sulfuric acid
With hydrogenchloride; sodium hydroxide; sulfuric acid In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; chloroform

N-(2-fluorophenyl)hydroxylamine (2369-21-3) → 2-chloro-6-fluoroaniline (363-51-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: NaHCO3 / diethyl ether; H2O / 1 h / T < 5 deg C; or in benzene 2: 75 percent / SOCl2 / diethyl ether / 1 h / T < 5 deg C 3: 71 percent / 70percent H2SO4 / 3 h / Heating View Scheme

N-(2-Fluorophenyl)benzohydroxamic acid (90493-82-6) → 2-chloro-6-fluoroaniline (363-51-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 75 percent / SOCl2 / diethyl ether / 1 h / T < 5 deg C 2: 71 percent / 70percent H2SO4 / 3 h / Heating View Scheme

ortho-nitrofluorobenzene (1493-27-2) → 2-chloro-6-fluoroaniline (363-51-9)

Conditions	Yield
Multi-step reaction with 4 steps 1: Zinc dust, NH4Cl (or NH4Br) 2: NaHCO3 / diethyl ether; H2O / 1 h / T < 5 deg C; or in benzene 3: 75 percent / SOCl2 / diethyl ether / 1 h / T < 5 deg C 4: 71 percent / 70percent H2SO4 / 3 h / Heating View Scheme

2-chloro-6-fluoroaniline (363-51-9) + (2-ethoxyphenyl)boronic acid (213211-69-9) → C14H14FNO

Conditions	Yield
With palladium diacetate; 2-dicyclohexylphosphino-2',6'-dimethylbiphenyl In toluene at 100℃; for 3h;	99%

2-chloro-6-fluoroaniline (363-51-9) + 4-nitro-benzoic acid (62-23-7) → C13H8ClFN2O3

Conditions	Yield
With covalent organic polymer from p-aminophenol and cyanuric chloride In 1,4-dioxane at 20℃; for 0.666667h;	94%

4-Cyanochlorobenzene (623-03-0) + 2-chloro-6-fluoroaniline (363-51-9) → 4-(2-chloro-6-fluorophenylamino)benzonitrile (817621-48-0)

Conditions	Yield
Stage #1: 2-chloro-6-fluoroaniline With sodium hydride In N,N-dimethyl-formamide at 0 - 4℃; for 1h; Stage #2: 4-Cyanochlorobenzene In N,N-dimethyl-formamide at 50 - 55℃; for 20h;	91%

para-bromotoluene (106-38-7) + 2-chloro-6-fluoroaniline (363-51-9) → N-(2-chloro-6-fluoro-phenyl)-4-methylaniline (332903-74-9)

Conditions	Yield
With tri-tert-butyl phosphine; sodium t-butanolate; bis(dibenzylideneacetone)-palladium(0) In toluene at 110℃; for 14h; Buchwald-Hartwig coupling;	90%

o-fluorobenzyl bromide (446-48-0) + 2-chloro-6-fluoroaniline (363-51-9) + potassium ethyl xanthogenate (140-89-6) → 4-fluoro-2-(2-fluoro-benzylsulfanyl)-benzothiazole

Conditions	Yield
Stage #1: 2-chloro-6-fluoroaniline; potassium ethyl xanthogenate In N,N-dimethyl-formamide at 120℃; for 0.25h; microwave irradiation; Stage #2: o-fluorobenzyl bromide In N,N-dimethyl-formamide at 90℃; for 0.1h; microwave irradiation;	90%

2-chloro-6-fluoroaniline (363-51-9) → 4-bromo-2-chloro-6-fluorobenzeneamine

Conditions	Yield
With bromine In chloroform	88%
With bromine In chloroform at 20℃; for 2h;	83%

2-chloro-6-fluoroaniline (363-51-9) + acetic anhydride (108-24-7) → N-(2-chloro-6-fluorophenyl)acetamide (343-73-7)

Conditions	Yield
With acetic acid at 90℃; for 2h;	88%
With acetic acid at 90℃; for 1h;
Stage #1: 2-chloro-6-fluoroaniline; acetic anhydride With acetic acid at 90℃; for 1h; Stage #2: With sodium hydroxide In water
With acetic acid at 90℃; for 2h;
With acetic acid at 90℃; for 2h;

2-chloro-6-fluoroaniline (363-51-9) + 4-bromo-2-butoxy-5-fluorobenzoic acid → 4-bromo-2-butoxy-N-(2-chloro-6-fluorophenyl)-5-fluorobenzamide

Conditions	Yield
Stage #1: 4-bromo-2-butoxy-5-fluorobenzoic acid With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide for 1h; Stage #2: 2-chloro-6-fluoroaniline With triethylamine In dichloromethane for 1h;	88%

2-chloro-6-fluoroaniline (363-51-9) + 2,6-Difluorobenzyl bromide (85118-00-9) + potassium ethyl xanthogenate (140-89-6) → 2-(2,6-difluoro-benzylsulfanyl)-4-fluoro-benzothiazole

Conditions	Yield
Stage #1: 2-chloro-6-fluoroaniline; potassium ethyl xanthogenate In N,N-dimethyl-formamide at 120℃; for 0.25h; microwave irradiation; Stage #2: 2,6-Difluorobenzyl bromide In N,N-dimethyl-formamide at 90℃; for 0.1h; microwave irradiation;	86%

2-chloro-6-fluoroaniline (363-51-9) + potassium ethyl xanthogenate (140-89-6) + alpha-bromo-3,4-difluorotoluene (85118-01-0) → 2-(3,4-difluoro-benzylsulfanyl)-4-fluoro-benzothiazole

Conditions	Yield
Stage #1: 2-chloro-6-fluoroaniline; potassium ethyl xanthogenate In N,N-dimethyl-formamide at 120℃; for 0.25h; microwave irradiation; Stage #2: alpha-bromo-3,4-difluorotoluene In N,N-dimethyl-formamide at 90℃; for 0.1h; microwave irradiation;	86%

2-chloro-6-fluoroaniline (363-51-9) + isopropyl 6-(3-((benzyloxy)methyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-2-(2-ethoxyvinyl)-5-fluoronicotinate → 2-(3-((benzyloxy)methyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-6-(2-chloro-6-fluorophenyl)-3-fluoro-1,6-naphthyridin-5(6H)-one

Conditions	Yield
Stage #1: 2-chloro-6-fluoroaniline With trimethylaluminum In dichloromethane at 0℃; for 0.0833333h; Inert atmosphere; Stage #2: isopropyl 6-(3-((benzyloxy)methyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-2-(2-ethoxyvinyl)-5-fluoronicotinate In dichloromethane; toluene at 20 - 50℃;	86%

2-chloro-6-fluoroaniline (363-51-9) + 4-bromo-5-fluoro-2-{[(2S)-1,1,1-trifluoropropan-2-yl]oxy}benzoyl chloride → 4-bromo-N-(2-chloro-6-fluorophenyl)-5-fluoro-2-{[(2S)-1,1,1-trifluoropropan-2-yl]oxy}benzamide

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 0.5h;	84.5%
With triethylamine In dichloromethane at 20℃; for 0.5h;	84.5%
With triethylamine In dichloromethane at 20℃; for 0.5h;	39.3 g
With triethylamine In dichloromethane at 25℃; for 16.5h;

2-chloro-6-fluoroaniline (363-51-9) + 2,4,5-trifluorobenzoyl chloride (88419-56-1) → N-(2-chloro-6-fluorophenyl)-2,4,5-trifluorobenzamide

Conditions	Yield
With pyridine In dichloromethane at 25℃; for 16h; Inert atmosphere;	83.43%

5-bromo-1,3-xylene (556-96-7) + 2-chloro-6-fluoroaniline (363-51-9) → (2-chloro-6-fluorophenyl)(3,5-dimethylphenyl)amine (1041144-10-8)

Conditions	Yield
With sodium t-butanolate; tri tert-butylphosphoniumtetrafluoroborate; palladium diacetate In toluene for 18h; Heating;	83%

2-chloro-6-fluoroaniline (363-51-9) + trifluoroacetic acid (76-05-1) → (Z)-N-(2-chloro-6-fluorophenyl)-2,2,2-trifluoroacetimidoyl chloride

Conditions	Yield
Stage #1: trifluoroacetic acid With tetrachloromethane; triethylamine; triphenylphosphine at 0℃; for 0.5h; Inert atmosphere; Stage #2: 2-chloro-6-fluoroaniline With tetrachloromethane at 80℃; for 3.16667h; Inert atmosphere;	82%

2-chloro-6-fluoroaniline (363-51-9) + 5-((benzyloxy)methyl)-4-ethyl-2-(7-fluoro-4-isopropyl-1-oxo-1H-isochromen-6-yl)-2,4-dihydro-3H-1,2,4-triazol-3-one → 6-(3-((benzyloxy)methyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-2-(2-chloro-6-fluorophenyl)-7-fluoro-4-isopropylisoquinolin-1(2H)-one

Conditions	Yield
Stage #1: 2-chloro-6-fluoroaniline With trimethylaluminum In dichloromethane at 20℃; for 0.5h; Inert atmosphere; Stage #2: 5-((benzyloxy)methyl)-4-ethyl-2-(7-fluoro-4-isopropyl-1-oxo-1H-isochromen-6-yl)-2,4-dihydro-3H-1,2,4-triazol-3-one In dichloromethane at 20℃; Inert atmosphere;	82%

4-chloroquinoline (611-35-8) + 2-chloro-6-fluoroaniline (363-51-9) → 10-fluoro-11H-indolo[3,2-c]quinoline (1111618-76-8)

Conditions	Yield
With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine In 1,4-dioxane; toluene at 125℃; for 24h; Inert atmosphere;	80%

2-chloro-6-fluoroaniline (363-51-9) + 2-methoxy-4,6-dimethylbenzeneboronic acid (355836-08-7) → C15H16FNO

Conditions	Yield
With palladium diacetate; 2-dicyclohexylphosphino-2',6'-dimethylbiphenyl In toluene at 100℃; for 1.5h;	80%

2-chloro-6-fluoroaniline (363-51-9) + isopropyl 6-(3-((benzyloxy)methyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-2-chloro-5-fluoronicotinate → 6-(3-((benzyloxy)methyl)-4-ethyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl)-2-chloro-N-(2-chloro-6-fluorophenyl)-5-fluoronicotinamide

Conditions	Yield
With trimethylaluminium In tetrahydrofuran; dichloromethane at 0 - 60℃; for 18.5h; Inert atmosphere;	79%

2-chloro-6-fluoroaniline (363-51-9) + (1-adamantyl)methyl isocyanate (69887-12-3) → 1-(adamantan-1-ylmethyl)-3-(6-chloro-2-fluorophenyl)urea

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 25℃; for 12h;	79%

2-chloro-6-fluoroaniline (363-51-9) + 4-bromo-5-fluoro-2-[(2S)-pentan-2-yloxy]benzoic acid → 4-bromo-N-(2-chloro-6-fluorophenyl)-5-fluoro-2-[(2S)-pentan-2-yloxy]benzamide

Conditions	Yield
Stage #1: 4-bromo-5-fluoro-2-[(2S)-pentan-2-yloxy]benzoic acid With 1-chloro-1-(dimethylamino)-2-methyl-1-propene In dichloromethane at 20℃; for 0.5h; Stage #2: 2-chloro-6-fluoroaniline With pyridine In dichloromethane at 20℃; for 1h;	78%

3,3-dimethyl acrylaldehyde (107-86-8) + 2-chloro-6-fluoroaniline (363-51-9) → N-(2-chloro-6-fluorophenyl)-3-methylbut-2-en-1-imine

Conditions	Yield
With titanium tetrachloride; triethylamine In dichloromethane at 0 - 25℃; for 5h; Inert atmosphere;	78%
With titanium tetrachloride; triethylamine In dichloromethane at 0 - 25℃; for 5h;

2-chloro-6-fluoroaniline (363-51-9) + (S)-7-(3-((benzyloxy)methyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-6-fluoro-1-(pentan-2-yl)-1H-benzo[d][1,3]oxazine-2,4-dione → (S)-4-(3-((benzyloxy)methyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol- 1-yl)-N-(2-chloro-6-fluorophenyl)-5-fluoro-2-(pentan-2-ylamino)benzamide

Conditions	Yield
Stage #1: 2-chloro-6-fluoroaniline With trimethylaluminium In toluene at 15℃; for 0.5h; Inert atmosphere; Stage #2: (S)-7-(3-((benzyloxy)methyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-6-fluoro-1-(pentan-2-yl)-1H-benzo[d][1,3]oxazine-2,4-dione In toluene at 50℃; for 16h; Inert atmosphere;	77%

2-chloro-6-fluoroaniline (363-51-9) + (5-methyl-2-oxo-cyclohexylidene)acetic acid ethyl ester (817621-74-2) → 1-(2-chloro-6-fluoro-phenyl)-5-methyl-1,4,5,6-tetrahydro-indol-2-one (817621-77-5)

Conditions	Yield
With toluene-4-sulfonic acid In toluene for 18h; Heating;	76%

2-chloro-6-fluoroaniline (363-51-9) + 2,4-dichloropyrimidine-5-carbonyl chloride (2972-52-3) → 2,4-dichloro-N-(2-chloro-6-fluorophenyl)pyrimidine-5-carboxamide

Conditions	Yield
In tetrahydrofuran at 20℃; for 15h; Inert atmosphere;	75%
In tetrahydrofuran at 20℃; for 15h; Inert atmosphere;	75%

3-methyl-2-pentenal (3592-19-6) + 2-chloro-6-fluoroaniline (363-51-9) → 6-(3-((benzyloxy)methyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-2-(2-chloro-6-fluorophenyl)-4-(3,3,3-trifluoroprop-1-en-2-yl)isoquinolin-1(2H)-one

Conditions	Yield
With titanium tetrachloride; triethylamine In dichloromethane at 0 - 20℃; for 5h; Inert atmosphere;	70%

3-methyl-2-pentenal (3592-19-6) + 2-chloro-6-fluoroaniline (363-51-9) → 2-chloro-6-fluoro-N-(3-methylpent-2-en-1-ylidene)aniline

Conditions	Yield
With titanium tetrachloride In dichloromethane at 0 - 20℃; for 5h; Inert atmosphere;	69.87%

2-chloro-6-fluoroaniline (363-51-9) + trifluoroacetic acid (76-05-1) → N-(2-chloro-6-hydroxyphenyl)-2,2,2-trifluoroacetamide

Conditions	Yield
With Oxone In 1,4-dioxane at 90℃; Schlenk technique; Inert atmosphere; chemoselective reaction;	65%

2-chloro-6-fluoroaniline (363-51-9) + 1-bromo-2,5-dimethoxy-3,4-dimethylbenzene (103323-61-1) → 1-fluoro-5,8-dimethoxy-6,7-dimethyl-9H-carbazole (1432270-58-0)

Conditions	Yield
With palladium diacetate; sodium t-butanolate; tri tert-butylphosphoniumtetrafluoroborate In toluene at 160℃; for 3h; Buchwald-Hartwig Coupling; Inert atmosphere; Microwave irradiation;	62%

Upstream product

• 90493-88-2 2'-Chloro-6'-fluorobenzanilide 
• 1493-27-2 ortho-nitrofluorobenzene 
• 90493-82-6 N-(2-Fluorophenyl)benzohydroxamic acid 
• 2369-21-3 N-(2-fluorophenyl)hydroxylamine 
• 434-75-3 2-chloro-6-fluorobenzoic acid 

Downstream Products

• 106976-11-8 N-(2-chloro-6-fluorophenyl)-3-nitroanthranilic acid 
• 817621-48-0 4-(2-chloro-6-fluorophenylamino)benzonitrile 
• 332903-74-9 N-(2-chloro-6-fluoro-phenyl)-4-methylaniline 
• 817621-77-5 1-(2-chloro-6-fluoro-phenyl)-5-methyl-1,4,5,6-tetrahydro-indol-2-one 
• 702640-40-2 2-fluoro-4-iodo-6-chloroaniline 
• 885453-49-6 4-bromo-2-chloro-6-fluorobenzeneamine 
• 34989-13-4 {BH-N(2.6-ClF-C₆H₃)}3 
• 1041143-45-6 1-fluoro-6-methyl-9H-carbazole 
• 1041144-10-8 (2-chloro-6-fluorophenyl)(3,5-dimethylphenyl)amine 
• 1239957-28-8 2-chloro-N-((5-(2-(3,4-dimethoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-iniidazol-2-yl)methyl)-6-fluoroaniline 
• 899806-25-8 1-chloro-3-fluoro-2-isothiocyanatobenzene 
• 1362477-26-6 4-(2-bromo-4-fluorophenyl)-N-(2-chloro-6-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine 
• 154327-24-9 4-fluorobenzothiazole-2(3H)-thione 
• 154327-25-0 4-fluoro-2-(methylthio)benzo[d]thiazole 

Relevant academic research and scientific papers

Novel Reactions: Part I - Facile Synthesis of Substituted ortho-Chloranilines from Nitrobenzene Derivatives

N-Substituted benzo and acetohydroxamic acids (5), prepared from N-arylhydroxylamines and benzoyl or acetyl chloride, react readily with thionyl chloride at low temperature to give ortho-chloroanilide derivatives (6) in good yield.The latter (6) on hydrolysis give ortho-chloroanilines (10).Since the N-arylhydroxylamines are obtained from nitroarenes by partial reduction, the overall reaction amounts to the preparation of 10 from nitroarenes.

2,3,4,4A-Tetrahydro-1H-pyrazino[1,2-a,]quinoxalin-5(6H)-ones and derivatives thereof for relieving hypertension

Compounds of the formula STR1 wherein R is hydrogen (lower)alkyl, phen(lower)alkyl, benzoyl(lower)alkyl, or p-halobenzoyl(lower)alkyl; R1 is hydrogen or (lower)alkyl; R2 is hydrogen, (lower)alkyl, (lower)alkoxy, chlorine, fluorine, trifluoromethyl, or amino in the 7-, 8-, or 9-position; R3 is hydrogen, or (lower)alkyl; and R4 is hydrogen, (lower)alkyl, (lower)alkoxy, chlorine, fluorine, or trifluoromethyl in the 7-, 8-, or 9-position; or the non-toxic acid addition salts thereof; exert a hypotensive effect in hypertensive animals.