2106-05-0

Basic information

• Product Name: 5-Chloro-2-fluoroaniline
• Synonyms: 5-Chloro-2-fluoroaniline, 97+%;BUTTPARK 44\01-98;5-CHLORO-2-FLUOROPHENYLAMINE;5-CHLORO-2-FLUOROANILINE;5-Chloro-2-fluoroaniline 98%;5-Chloro-2-fluoroaniline98%;5-Chloro-2-fluoroani
• CAS NO: 2106-05-0
• Molecular Formula: C₆H₅ClFN
• Molecular Weight: 145.56
• EINECS: 218-284-1
• Product Categories: Building Blocks;C6;Chemical Synthesis;Fluorinated Building Blocks;Nitrogen Compounds;Organic Building Blocks;Organic Fluorinated Building Blocks;Other Fluorinated Organic Building Blocks;Fluorine series;Anilines, Aromatic Amines and Nitro Compounds;Aniline;Miscellaneous;Amines;Aryl Fluorinated Building Blocks
• Mol File: 2106-05-0.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 102-105 °C20 mm Hg(lit.)
• Flash Point: 219 °F
• Appearance: /
• Density: 1.29 g/mL at 25 °C(lit.)
• Vapor Pressure: 0.0567mmHg at 25°C
• Refractive Index: n20/D 1.561(lit.)
• Storage Temp.: Keep in dark place,Inert atmosphere,Room temperature
• PKA: 2.15±0.10(Predicted)
• CAS DataBase Reference: 5-Chloro-2-fluoroaniline(CAS DataBase Reference)
• NIST Chemistry Reference: 5-Chloro-2-fluoroaniline(2106-05-0)
• EPA Substance Registry System: 5-Chloro-2-fluoroaniline(2106-05-0)

Safety Data

• Hazard Codes: Xi,T,Xn
• Statements: 36/37/38-20/21/22-23/24/25
• Safety Statements: 26-36-2636/37/39-23-36/37/39-45
• RIDADR: UN2810
• WGK Germany: 3
• HazardClass: 6.1
• PackingGroup: III
• Hazardous Substances Data: 2106-05-0(Hazardous Substances Data)

Usage

Chemical Properties

Colorless liquid

InChI:InChI=1/C6H3ClFNO2/c7-4-2-1-3-5(6(4)8)9(10)11/h1-3H

Synthetic route

2-fluoro-5-chloronitrobenzene (345-18-6) → 5-chloro-2-fluoroaniline (2106-05-0)

Conditions	Yield
With hydrogen; platinum on activated charcoal In 1,2-dimethoxyethane under 2585.74 Torr; for 24h; Catalytic hydrogenation;

2,5-dichloronitrobenzene (89-61-2) + potassium-compound of 1-<4-hydroxy-phenyl>-ethanone → 5-chloro-2-fluoroaniline (2106-05-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 52 percent / KF; 18-crown-6 / tetrahydrothiophene 1,1-dioxide / 32 h / 180 °C 2: H2 / 5 percent Pt/C / 1,2-dimethoxy-ethane / 24 h / 2585.74 Torr View Scheme

2-fluoro-5-chloronitrobenzene (345-18-6) → 2-Fluoroaniline (348-54-9) + 5-chloro-2-fluoroaniline (2106-05-0)

Conditions	Yield
With 5%-palladium/activated carbon; hydrazine hydrate In methanol at 80℃; for 0.0833333h; Overall yield = 25 %;

C15H14ClFN2 → 5-chloro-2-fluoroaniline (2106-05-0)

Conditions	Yield
With sodium tetrahydroborate; copper(l) chloride In ethanol at 20℃;	24 mg

3,3'-dichloroazobenzene (15426-14-9, 106131-20-8, 106131-24-2) → 5-chloro-2-fluoroaniline (2106-05-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: bis(dibenzylideneacetone)-palladium(0); N-fluorobis(benzenesulfon)imide; potassium nitrate / ethyl acetate / 12 h / 90 °C / Sealed tube 2: sodium tetrahydroborate; copper(l) chloride / ethanol / 20 °C View Scheme

1-(3-chlorophenyl)-2-(2,4,6-trimethylphenyl)diazene → 5-chloro-2-fluoroaniline (2106-05-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: bis(dibenzylideneacetone)-palladium(0); N-fluorobis(benzenesulfon)imide; potassium nitrate / ethyl acetate / 12 h / 100 °C / Sealed tube 2: sodium tetrahydroborate; copper(l) chloride / ethanol / 20 °C View Scheme

C12H7Cl2FN2 → 5-chloro-2-fluoroaniline (2106-05-0)

Conditions	Yield
With sodium tetrahydroborate; copper(l) chloride In ethanol at 20℃;	28.8 mg

5-chloro-2-fluoroaniline (2106-05-0) → C6H4ClFIN

Conditions	Yield
With iodine; silver sulfate In ethanol at 0 - 20℃; for 1h; Large scale;	98%

methyl 3-(3-{2-[(3-{[2-(dimethylamino)ethyl]oxy}phenyl)amino]-4-pyrimidinyl}-imidazo[1,2-a]pyridin-2-yl)benzoate (1089278-78-3) + 5-chloro-2-fluoroaniline (2106-05-0) → N-(5-chloro-2-fluorophenyl)-3-(3-{2-[(3-{[2-(dimethylamino)ethyl]oxy}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)benzamide (1089278-77-2)

Conditions	Yield
Stage #1: methyl 3-(3-{2-[(3-{[2-(dimethylamino)ethyl]oxy}phenyl)amino]-4-pyrimidinyl}-imidazo[1,2-a]pyridin-2-yl)benzoate; 5-chloro-2-fluoroaniline With sodium hexamethyldisilazane In tetrahydrofuran at 20℃; for 0.5h; Stage #2: With methanol In tetrahydrofuran	94%

5-chloro-2-fluoroaniline (2106-05-0) → 4-bromo-5-chloro-2-fluoroaniline (116369-24-5)

Conditions	Yield
With N-Bromosuccinimide In acetonitrile at 25℃; for 1h;	91%

4,7-dichloroquinoline (86-98-6) + 5-chloro-2-fluoroaniline (2106-05-0) → 4-(5'-chloro-2'-fluorophenyl)amino-7-chloroquinoline

Conditions	Yield
for 0.0583333h; microwave irradiation;	90%

5-chloro-2-fluoroaniline (2106-05-0) + Propiolic acid (471-25-0) → N-(5-chloro-2-fluorophenyl)prop-2-ynamide

Conditions	Yield
With dicyclohexyl-carbodiimide In toluene at 5℃; for 2h;	88%

2-(chloromethyl)-8-((2-chloro-5-thiazolyl)methyl)-1,4-dioxa-8-azaspiro[4,5]decane (1246443-58-2) + 5-chloro-2-fluoroaniline (2106-05-0) → N-(5-chloro-2-fluorophenyl)-N-({8-((2-chloro-5-thiazolyl)methyl)-1,4-dioxa-8-aza-spiro[4,5]dec-2-yl}methyl)amine (1246443-53-7)

Conditions	Yield
With potassium carbonate; potassium iodide In N,N-dimethyl-formamide at 28 - 140℃;	85%
With potassium carbonate; potassium iodide In N,N-dimethyl-formamide at 140℃; for 20h;	85%

5-chloro-2-fluoroaniline (2106-05-0) + 1,3-cylohexanedione (504-02-9) → 3-(5-chloro-2-fluorophenylamino)cyclohex-2-enone

Conditions	Yield
In 1,2-dichloro-ethane at 25 - 30℃; for 8h;	85%

5-chloro-2-fluoroaniline (2106-05-0) + tin(ll) chloride → (5-Chloro-2-fluoro-phenyl)-hydrazine (396074-99-0)

Conditions	Yield
With sodium nitrite In hydrogenchloride; water	83%

5-chloro-2-fluoroaniline (2106-05-0) + bis(pinacol)diborane (73183-34-3) → 2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (1003575-43-6)

Conditions	Yield
With tris(trimethylphosphine)nickel(II) chloride; (2,2,2-trifluoroethoxy)trimethylsilane; cesium fluoride In tetrahydrofuran at 100℃; for 12h; Inert atmosphere;	81%
With (2,2,2-trifluoroethoxy)trimethylsilane; cesium fluoride; dichlorobis(trimethylphosphine)nickel In tetrahydrofuran at 100℃; for 12h; Inert atmosphere; Sealed tube;	81%

5-chloro-2-fluoroaniline (2106-05-0) + bis-(2-chloroethyl)amine hydrochloride (821-48-7) → 1-(5-Chloro-2-fluorophenyl)-piperazine

Conditions	Yield
In 1,2-dichloro-benzene; hexan-1-ol for 11h; Heating / reflux;	76.6%

C7H6ClN3OS (357204-44-5) + 5-chloro-2-fluoroaniline (2106-05-0) → 1-(5-chloro-2-fluorophenyl)-3-(5-chloro-1,3-dimethyl-1H-pyrazole-4-carbonyl)thiourea (1392131-61-1)

Conditions	Yield
In tetrahydrofuran at 20℃; for 4h;	72.1%

5-chloro-2-fluoroaniline (2106-05-0) + (S)-(–)-1-isocyanato-4,7,7-trimethyl-2-oxabicyclo[2.2.1]heptan-3-one → N-(5-chloro-2-fluorophenyl)-N′-{(S)-(–)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptan-1-yl}-urea

Conditions	Yield
With triethylamine In diethyl ether at 20℃; for 12h;	72%

trimethylsilyl isothiocyanate (2290-65-5) + 5-chloro-2-fluoroaniline (2106-05-0) + para-bromophenacyl bromide (99-73-0) → C15H9BrClFN2S*BrH (1449223-29-3)

Conditions	Yield
In ethanol at 70℃;	69%

5-chloro-2-fluoroaniline (2106-05-0) + trifluoroacetic acid (76-05-1) → N-(5-chloro-2-hydroxyphenyl)trifluoroacetamide (93416-35-4)

Conditions	Yield
With Oxone In 1,4-dioxane at 90℃; Schlenk technique; Inert atmosphere; chemoselective reaction;	66%

5-chloro-2-fluoroaniline (2106-05-0) + Cinnamic acid (621-82-9) → (2E)-N-(5-chloro-2-fluorophenyl)-3-phenylprop-2-enamide

Conditions	Yield
With phosphorus trichloride In chlorobenzene at 130℃; for 0.5h; Microwave irradiation;	59%

5-chloro-2-fluoroaniline (2106-05-0) + C13H6ClFN2O3 → N-(5-chloro-2-fluorophenyl)-2-fluoro-5-(5-(furan-2-yl)-1,3,4-oxadiazol-2-yl)benzamide

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃; for 12h;	52.8%

5-chloro-2-fluoroaniline (2106-05-0) + 4-chloro-7-methoxy-6-(3-morpholinopropoxy)quinazoline (199327-59-8) → 4-[(5-chloro-2-fluorophenyl)amino]-6-[3-(morpholin-4-yl)propyloxy]-7-methoxyquinazoline (909863-34-9)

Conditions	Yield
With acetic acid at 80℃; for 7h;	42%

5-chloro-2-fluoroaniline (2106-05-0) → 2-fluoro-5-chlorophenol

Conditions	Yield
Stage #1: 5-chloro-2-fluoroaniline With sulfuric acid; sodium nitrite In water at -5 - -2℃; for 0.5h; Stage #2: With sulfuric acid; copper(II) sulfate In water at 160℃; for 2h;	40%

5-chloro-2-fluoroaniline (2106-05-0) → 2-fluoro-5-chlorophenol + phenol (108-95-2)

Conditions	Yield
With copper(II) sulfate; sodium nitrite In sulfuric acid; water	A n/a B 40%

5-chloro-2-fluoroaniline (2106-05-0) + 4-chloro-7-iodo-6-nitroquinazoline → N-(5-chloro-2-fluorophenyl)-7-iodo-6-nitroquinazolin-4-amine

Conditions	Yield
With formic acid In dichloromethane; isopropyl alcohol at 0 - 20℃; for 0.5h;	37%

4-(4-aminophenoxy)-N-methylpyridine-2-carboxamide (284462-37-9) + 5-chloro-2-fluoroaniline (2106-05-0) + 1,1'-carbonyldiimidazole (530-62-1) → 4-(4-(3-(5-chloro-2-fluorophenyl)ureido)phenoxy)-N-methylpicolinamide (1290546-55-2)

Conditions	Yield
Stage #1: 5-chloro-2-fluoroaniline; 1,1'-carbonyldiimidazole In dichloromethane at 20℃; for 22.1667h; Stage #2: 4-(4-aminophenoxy)-N-methylpyridine-2-carboxamide In dichloromethane for 4h;	35%

1-adamantyl isocyanate (4411-25-0) + 5-chloro-2-fluoroaniline (2106-05-0) → N,N'-bis(1-adamantyl)urea (29559-44-2) + 1-(adamantan-1-yl)-3-(5-chloro-2-fluorophenyl)urea

Conditions	Yield
With triethylamine In diethyl ether at 20℃; for 12h; Curtius Rearrangement;	A n/a B 35%

5-chloro-2-fluoroaniline (2106-05-0) + 5-isocyanatoadamantan-2-one → N-(5-chloro-2-fluorophenyl)-N′-(4-oxoadamantan-1-yl)urea

Conditions	Yield
With triethylamine In diethyl ether at 20℃; for 12h;	33%

2-bromo-3-nitro-benzoic acid (573-54-6) + 5-chloro-2-fluoroaniline (2106-05-0) → 2-(5-Chloro-2-fluoro-phenylamino)-3-nitro-benzoic acid (103942-81-0)

Conditions	Yield
With N-ethylmorpholine;; copper; copper(l) chloride In various solvent(s) at 70 - 80℃; for 15h;	31%
With N-ethylmorpholine;; copper; copper(l) chloride In various solvent(s) at 70℃; for 18h; Yield given;

5-(3-hydroxyphenyl)isoxazole-3-carboxylic acid (832740-37-1) + 5-chloro-2-fluoroaniline (2106-05-0) → N-(5-chloro-2-fluorophenyl)-5-(3-hydroxyphenyl)isoxazole-3-carboxamide

Conditions	Yield
Stage #1: 5-(3-hydroxyphenyl)isoxazole-3-carboxylic acid With thionyl chloride In tetrahydrofuran for 0.5h; Reflux; Stage #2: 5-chloro-2-fluoroaniline With triethylamine In tetrahydrofuran at 20 - 35℃; for 2h;	24%

5-chloro-2-fluoroaniline (2106-05-0) → N-(5-chloro-2-fluorophenyl)iminodiacetic acid (1190891-89-4)

Conditions	Yield
	22%

5-chloro-2-fluoroaniline (2106-05-0) + tert-butyl 5-chloropyrazolo[1,5-a]pyrimidin-7-yl(2-morpholinopropyl)carbamate → N5-(5-chloro-2-fluorophenyl)-N7-(2-morpholinopropyl)pyrazolo[1,5-a]pyrimidine-5,7-diamine

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); lithium hexamethyldisilazane; XPhos In tetrahydrofuran; dichloromethane at 65℃; for 1h; Sealed tube;	21%

5-chloro-2-fluoroaniline (2106-05-0) + 5-(3-hydroxy-4-methoxyphenyl)isoxazole-3-carboxylic acid → N-(5-chloro-2-fluorophenyl)-5-(3-hydroxy-4-methoxyphenyl)isoxazole-3-carboxamide

Conditions	Yield
Stage #1: 5-(3-hydroxy-4-methoxyphenyl)isoxazole-3-carboxylic acid With thionyl chloride In tetrahydrofuran for 0.5h; Reflux; Stage #2: 5-chloro-2-fluoroaniline With triethylamine In tetrahydrofuran at 20 - 35℃; for 2h;	20%

1-(azidomethyl)-4-methoxybenzene (70978-37-9) + 5-chloro-2-fluoroaniline (2106-05-0) + 3-fluoro-4-(3,3,3-trifluoroprop-1-yn-1-yl)pyridine → N-(5-chloro-2-fluorophenyl)-4-[5-(trifluoromethyl)-1H-1,2,3-triazol-4-yl]pyridin-3-amine

Conditions	Yield
Stage #1: 1-(azidomethyl)-4-methoxybenzene; 3-fluoro-4-(3,3,3-trifluoroprop-1-yn-1-yl)pyridine In tert-butyl methyl ether; tert-butyl alcohol at 80℃; for 2h; Stage #2: 5-chloro-2-fluoroaniline With potassium carbonate In dimethyl sulfoxide at 180℃; for 5h; Stage #3: With trifluoroacetic acid at 50℃;	17%

3-methylenebutanedioyl dichloride (1931-60-8) + 5-chloro-2-fluoroaniline (2106-05-0) → 4-((5-chloro-2-fluorophenyl)amino)-2-methylene-4-oxobutanoic acid + N,N'-bis(5-chloro-2-fluorophenyl)-2-methylenesuccinamide

Conditions	Yield
In dichloromethane at -4 - 20℃; Molecular sieve;	A 9.9% B 11.7%

Upstream product

• 15426-14-9 3,3'-dichloroazobenzene 
• 345-18-6 2-fluoro-5-chloronitrobenzene 
• 89-61-2 2,5-dichloronitrobenzene 

Downstream Products

• 396074-99-0 (5-Chloro-2-fluoro-phenyl)-hydrazine 
• 290330-94-8 C₁₂H₈Cl₂FNO₂S 
• 909863-42-9 C₂₅H₂₈ClFN₄O₄ 
• 29559-44-2 N,N'-bis(1-adamantyl)urea 
• 861393-72-8 N-(5-chloro-2-fluorophenyl)-N''-cyanoguanidine 
• 1089278-77-2 N-(5-chloro-2-fluorophenyl)-3-(3-{2-[(3-{[2-(dimethylamino)ethyl]oxy}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)benzamide 
• 108-95-2 phenol 
• 704-11-0 5-chloro-2-fluoro-4-nitro-aniline 
• 133117-00-7 2-chloro-4,5-difluoro-α-chloroacetophenone 
• 121872-94-4 2'-chloro-4',5'-difluoroacetophenone 
• 110877-64-0 2-chloro-4,5-difluorobenzoic acid 
• 696-02-6 4-chloro-1,2-difluorobenzene 
• 103942-81-0 2-(5-Chloro-2-fluoro-phenylamino)-3-nitro-benzoic acid 
• 717-04-4 acetic acid-(5-chloro-2-fluoro-4-nitro-anilide) 

Relevant articles and documents

Anion ligand promoted selective C-F bond reductive elimination enables C(sp2)-H fluorination

A detailed mechanism study on the anion ligand promoted selective C-H bond fluorination is reported. The role of the anion ligand has been clarified by experimental evidence and DFT calculations. Moreover, the nitrate promoted C-F bond reductive elimination enabled a selective C-H bond fluorination of various symmetric and asymmetric azobenzenes to access diverse o-fluoroanilines.

SYNTHESIS OF 2-HALO-4,5-DIFLUOROBENZOIC ACIDS

-