57946-56-2

Basic information

• Product Name: 4-Chloro-2-fluoroaniline
• Synonyms: 4-CHLORO-2-FLUOROANILINE;4-CHLORO-2-FLUOROBENZENAMINE;4-CHLORO-2-FLUORO-PHENYLAMINE;2-FLUORO-4-CHLOROANILINE;TIMTEC-BB SBB004111;4-Chloro-2-fluoroaniline,98%;4-Chloro-2-fluoroaniline 98%;-Chloro-2-fluoroaniline
• CAS NO: 57946-56-2
• Molecular Formula: C₆H₅ClFN
• Molecular Weight: 145.56
• EINECS: 261-034-1
• Product Categories: Anilines, Aromatic Amines and Nitro Compounds;Aniline;Fluorobenzene;Anilines, Amides & Amines;Chlorine Compounds;Fluorine Compounds;Amines;C2 to C6;Nitrogen Compounds;Aryl Fluorinated Building Blocks;Building Blocks;C6;Chemical Synthesis;Fluorinated Building Blocks;Nitrogen Compounds;Organic Building Blocks;Organic Fluorinated Building Blocks;Other Fluorinated Organic Building Blocks
• Mol File: 57946-56-2.mol
• Article Data: 21

Chemical Properties

• Boiling Point: 104-107 °C (28 mmHg)
• Flash Point: 210 °F
• Appearance: Clear slightly yellow to orange-brown/Liquid
• Density: 1.311 g/mL at 25 °C(lit.)
• Refractive Index: n20/D 1.56(lit.)
• Storage Temp.: Room temperature.
• PKA: 2.57±0.10(Predicted)
• Water Solubility: slightly soluble
• BRN: 1934804
• CAS DataBase Reference: 4-Chloro-2-fluoroaniline(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Chloro-2-fluoroaniline(57946-56-2)
• EPA Substance Registry System: 4-Chloro-2-fluoroaniline(57946-56-2)

Safety Data

• Hazard Codes: Xn,T,Xi
• Statements: 20/21/22-36/37/38-23/24/25
• Safety Statements: 26-37/39-36/37/39-45
• RIDADR: 2810
• WGK Germany: 3
• HazardClass: 6.1
• PackingGroup: III
• Hazardous Substances Data: 57946-56-2(Hazardous Substances Data)

Usage

Description

4-Chloro-2-fluoroaniline is an organic compound characterized by the presence of a chlorine atom at the 4th position and a fluorine atom at the 2nd position on an aniline molecule. It is a clear slightly yellow to orange-brown liquid and is primarily utilized in the synthesis of various chemical compounds.

Uses

Used in Pharmaceutical Industry:
4-Chloro-2-fluoroaniline is used as a synthetic intermediate for the production of 4-Chloro-2-fluoro-3-iodobenzenamine (1000590-87-3), which is an important compound in the pharmaceutical industry. This intermediate is crucial for the development of new drugs and therapeutic agents.
Used in Chemical Synthesis:
In the field of chemical synthesis, 4-Chloro-2-fluoroaniline serves as a key building block for the creation of various organic compounds. Its unique structure allows for further functionalization and modification, making it a valuable asset in the synthesis of complex molecules.
Used in Research and Development:
4-Chloro-2-fluoroaniline is also employed in research and development laboratories for the study of its chemical properties and potential applications. Its reactivity and structural features make it an interesting subject for scientific investigation, which may lead to the discovery of new compounds and applications.

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

Synthetic route

4'-chloro-2'-fluoroacetanilide (59280-70-5) → 2-fluoro-4-chloroaniline (57946-56-2)

Conditions	Yield
With sodium hydroxide; water In ethanol for 3h; Reflux;	95.6%
With sodium hydroxide In ethanol; water
With sodium hydroxide In ethanol; water

2-Fluoroaniline (348-54-9) → 2-fluoro-4-chloroaniline (57946-56-2)

Conditions	Yield
With copper dichloride; 1-hexyl-3-methylimidazol-1-ium chloride at 40℃; for 4h; regioselective reaction;	88%
With iron(III) chloride; N-chloro-succinimide; 1-butyl-3-methylimidazolium trifluoromethanesulfonimide In tetrahydrofuran at 60℃; for 18h; Inert atmosphere; regioselective reaction;	75%

4-chloro-2-fluorobenzoic acid (446-30-0) → 2-fluoro-4-chloroaniline (57946-56-2)

Conditions	Yield
With sodium azide; sulfuric acid

4-chloro-aniline (106-47-8) → 2-fluoro-4-chloroaniline (57946-56-2) + 4-chloro-3-fluoroaniline (367-22-6) + 4-chloro-3,5-difluorobenzenamine (2613-33-4) + 4-chloro-2,5-difluoroaniline (2613-30-1)

Conditions	Yield
With trifluorormethanesulfonic acid; fluorine at 20℃; Further byproducts given. Title compound not separated from byproducts;

CH3 NO2 + 4-chloro-2-fluorobenzoic acid (446-30-0) → 2-fluoro-4-chloroaniline (57946-56-2)

Conditions	Yield
With sodium hydroxide; PPA

N-(2-fluorophenyl)acetamide (399-31-5) → 2-fluoro-4-chloroaniline (57946-56-2) + 4'-chloro-2'-fluoroacetanilide (59280-70-5)

Conditions	Yield
With chlorine In acetic acid
With chlorine In acetic acid
With chlorine In acetic acid

4-chloro-2-fluoro-nitrobenzene (700-37-8) → 2-fluoro-4-chloroaniline (57946-56-2)

Conditions	Yield
With 2 wt% Pd/C; hydrogen at 120℃; under 7500.75 Torr;

C15H14ClFN2 → 2-fluoro-4-chloroaniline (57946-56-2)

Conditions	Yield
With sodium tetrahydroborate; copper(l) chloride In ethanol at 20℃;	23.6 mg

bis-(4-chloro-phenyl)-diazene (1602-00-2) → 2-fluoro-4-chloroaniline (57946-56-2)

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

C15H15ClN2 → 2-fluoro-4-chloroaniline (57946-56-2)

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 → 2-fluoro-4-chloroaniline (57946-56-2)

Conditions	Yield
With sodium tetrahydroborate; copper(l) chloride In ethanol at 20℃;	28.4 mg

2-fluoro-4-chloroaniline (57946-56-2) + ethyl 4-chloro-6,7-dimethoxyquinoline-3-carboxylate (26893-14-1) → ethyl 4-((4-chloro-2-fluorophenyl)amino)-6,7-dimethoxyquinoline-3-carboxylate

Conditions	Yield
In isopropyl alcohol at 20 - 100℃; for 16h; Inert atmosphere;	99%

2-fluoro-4-chloroaniline (57946-56-2) + 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1) → (4-chloro-2-fluoro-phenyl)-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine (865364-20-1)

Conditions	Yield
With silver trifluoromethanesulfonate In N,N-dimethyl-formamide at 90℃;	98%

2-thienylacetic acid chloride (39098-97-0) + 2-fluoro-4-chloroaniline (57946-56-2) → C12H9ClFNOS

Conditions	Yield
In tetrahydrofuran at 20℃;	98%

4-Chloro-6-cyano-7-(2-methoxyethoxy)quinoline hydrochloride (205448-26-6) + 2-fluoro-4-chloroaniline (57946-56-2) → 4-(4-chloro-2-fluoroanilino)-6-cyano-7-(2-methoxyethoxy)quinoline hydrochloride (205447-78-5)

Conditions	Yield
In isopropyl alcohol for 3h; Heating / reflux;	98%

tert-butyl 4-{[(4-chloro-6-methoxyquinazolin-7-yl)oxy]methyl}piperidine-1-carboxylate (401811-89-0) + 2-fluoro-4-chloroaniline (57946-56-2) → 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(piperidin-4-ylmethoxy)quinazoline (338992-08-8)

Conditions	Yield
With hydrogenchloride In 1,4-dioxane; isopropyl alcohol for 4h; Heating / reflux;	98%

2-fluoro-4-chloroaniline (57946-56-2) → 4-chloro-2-fluoro-6-iodophenylamine (216393-67-8)

Conditions	Yield
With silver(II) sulfate; iodine In ethanol at 20℃; for 2h;	98%
With trifluorormethanesulfonic acid; bis(pyridine)iodonium(I) tetrafluoroborate In dichloromethane	91%
With iodine; silver sulfate In ethanol at 20℃; for 1.5h;	87%

isopropanolic hydrogen chloride + 4-chloro-6-methoxy-7-(3-morpholinopropoxy)cinnoline hydrochloride + 2-fluoro-4-chloroaniline (57946-56-2) → 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(3-morpholinopropoxy)cinnoline hydrochloride

Conditions	Yield
In (+/-)-2-pentanol; isopropyl alcohol	98%

2-fluoro-4-chloroaniline (57946-56-2) → (4-chloro-2-fluorophenyl)hydrazine hydrochloride

Conditions	Yield
Stage #1: 2-fluoro-4-chloroaniline With barium nitrite In water at 45℃; Acidic conditions; Flow reactor; Stage #2: With potassium bisulfite In water at 60 - 89℃; Stage #3: With hydrogenchloride In water at 85℃;	97.2%
Stage #1: 2-fluoro-4-chloroaniline With hydrogenchloride In water at 0℃; Stage #2: With sodium nitrite In water at 0 - 20℃; Stage #3: With hydrogenchloride; tin(II) chloride dihdyrate In water at 0 - 20℃; for 4.5h;	62%

2-fluoro-4-chloroaniline (57946-56-2) + acetic anhydride (108-24-7) → 4'-chloro-2'-fluoroacetanilide (59280-70-5)

Conditions	Yield
In acetic acid at 20℃; for 2h;	95%
With acetic acid at 20℃; for 2h;	95%
With pyridine at 120℃; for 2h;
In acetic acid at 20℃; for 3h;

2-fluoro-4-chloroaniline (57946-56-2) + chloroformic acid ethyl ester (541-41-3) → ethyl N-(4-chloro-2-fluorophenyl)carbamate (114108-90-6)

Conditions	Yield
With pyridine at 0℃; for 3h;	95%
With hydrogenchloride In pyridine

2-fluoro-4-chloroaniline (57946-56-2) + benzoyl chloride (98-88-4) → N-(4-chloro-2-fluorophenyl)benzamide

Conditions	Yield
With triethylamine In tetrahydrofuran for 16h;	95%

2-fluoro-4-chloroaniline (57946-56-2) + 2,6-difluorobenzaldehyde (437-81-0) → (E)-N-(4-chloro-2-fluorophenyl)-1-(2,6-difluorophenyl)methanimine

Conditions	Yield
In toluene at 110℃; for 96h; Dean-Stark;	95%

2-fluoro-4-chloroaniline (57946-56-2) + 7-benzyloxy-4-chloro-6-methoxyquinazoline (162364-72-9) → 7-benzyloxy-4-(4-chloro-2-fluorophenylamino)-6-methoxyquinazoline hydrochloride

Conditions	Yield
With hydrogenchloride In isopropyl alcohol for 2h; Reflux;	94%
In isopropyl alcohol	64%
In isopropyl alcohol for 1.5h; Heating / reflux;	64%

2-fluoro-4-chloroaniline (57946-56-2) + acetic acid (64-19-7) → 4'-chloro-2'-fluoroacetanilide (59280-70-5)

Conditions	Yield
In acetic acid at 25℃; for 2h;	94%
With acetic anhydride at 25℃; for 2h;

1,1,1,2,2,2-hexamethyldisilane (1450-14-2) + 2-fluoro-4-chloroaniline (57946-56-2) → 2-fluoro-4-trimethylsilanylphenylamine (955372-99-3)

Conditions	Yield
With potassium fluoride; Pd(dibenzylideneacetone)2 chloroform adduct; dicyclohexylphenylphosphine In 1,4-dioxane at 100℃; for 18h;	93%

2-fluoro-4-chloroaniline (57946-56-2) + Ethyl oxalyl chloride (4755-77-5) → N-(2-fluoro-4-chlorophenyl)oxalamic acid ethyl ester

Conditions	Yield
With triethylamine In tetrahydrofuran at 20℃; for 12h;	92%
With triethylamine In tetrahydrofuran at 0 - 20℃; Inert atmosphere;	90%

2-fluoro-4-chloroaniline (57946-56-2) + 2,5-hexanedione (110-13-4) → 1-(4-chloro-2-fluorophenyl)-2,5-dimethyl-1H-pyrrole

Conditions	Yield
With toluene-4-sulfonic acid In toluene for 2h; Reflux;	92%
With aminosulfonic acid at 20℃; for 3h;

2-fluoro-4-chloroaniline (57946-56-2) + trans-4-methoxy-3-buten-2-one (51731-17-0) → (Z)-4-((4-chloro-2-fluorophenyl)amino)-but-3-en-2-one

Conditions	Yield
In water at 60℃; for 0.5h;	92%

ethereal hydrogen chloride + 2-fluoro-4-chloroaniline (57946-56-2) + 4,7-dichloro-6-nitro-quinazoline (162012-71-7) → 7-chloro-4-(4-chloro-2-fluoroanilino)-6-nitroquinazoline hydrochloride (205194-09-8)

Conditions	Yield
In isopropyl alcohol	90%

2-fluoro-4-chloroaniline (57946-56-2) + methyl 2-azido-2-benzamidoacetate (194365-76-9) → methyl 2-benzamido-2-(4-chloro-2-fluorophenylamino)acetate (1258422-70-6)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetone at 20℃; for 48h;	90%

3,3,3-Trifluoropropionic acid (2516-99-6) + 2-fluoro-4-chloroaniline (57946-56-2) → N-(4-chloro-2-fluoro-phenyl)-3,3,3-trifluoro-propionamide (1538626-78-6)

Conditions	Yield
With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In dichloromethane	90%
With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In dichloromethane	90%
With triethylamine; HATU In dichloromethane

di-tert-butyl dicarbonate (24424-99-5) + 2-fluoro-4-chloroaniline (57946-56-2) → tert-butyl (4-chloro-2-fluorophenyl)carbamate (956828-47-0)

Conditions	Yield
In 1,4-dioxane for 48h; Reflux;	89%
In 1,4-dioxane for 48h; Reflux;	89%
In 1,4-dioxane for 48h; Reflux;	89%

2-fluoro-4-chloroaniline (57946-56-2) + 4-methoxy-benzoyl chloride (100-07-2) → N-(4-chloro-2-fluorophenyl)-4-methoxybenzamide

Conditions	Yield
With triethylamine In tetrahydrofuran for 16h;	88%

2-fluoro-4-chloroaniline (57946-56-2) + 2-((5-bromo-2-chloropyrimidin-4-yl)oxy)-N-methylbenzamide → 2-((5-bromo-2-((4-chloro-2-fluorophenyl)amino)pyrimidin-4-yl)oxy)-N-methylbenzamide

Conditions	Yield
With toluene-4-sulfonic acid In tetrahydrofuran at 80℃;	88%

isatoic anhydride (118-48-9) + 2-fluoro-4-chloroaniline (57946-56-2) → 3-(4-chloro-2-fluorophenyl)quinazolin-4(3H)-one

Conditions	Yield
With triethylamine sulfate; orthoformic acid triethyl ester In neat (no solvent) at 20℃; Niementowski Quinazolone Synthesis;	88%

cuprous (I) chloride + 2-fluoro-4-chloroaniline (57946-56-2) → 4-chloro-2-fluorobenzenesulfonyl chloride (141337-26-0)

Conditions	Yield
With hydrogenchloride; acetic acid; sodium nitrite In water	87.1%

2-fluoro-4-chloroaniline (57946-56-2) + 4-chloro-2-fluoro-phenyl isothiocyanate (68034-69-5) → N,N'-Di(2-fluoro-4-chlorophenyl)thiourea (354151-70-5)

Conditions	Yield
In ethanol at 20℃;	87%
In ethanol at 20℃; for 8h;

2-fluoro-4-chloroaniline (57946-56-2) → 4-chloro-2-fluoro-5-nitroaniline (86988-02-5)

Conditions	Yield
With nitric acid In sulfuric acid	86%
With nitric acid In sulfuric acid	86%
With nitric acid In sulfuric acid
With nitric acid In sulfuric acid
With sulfuric acid; nitric acid

Upstream product

• 446-30-0 4-chloro-2-fluorobenzoic acid 
• 106-47-8 4-chloro-aniline 
• 59280-70-5 4'-chloro-2'-fluoroacetanilide 
• 1602-00-2 bis-(4-chloro-phenyl)-diazene 
• 700-37-8 4-chloro-2-fluoro-nitrobenzene 
• 348-54-9 2-Fluoroaniline 
• 399-31-5 N-(2-fluorophenyl)acetamide 

Downstream Products

• 57381-51-8 4-chloro-2-fluorobenzonitrile 
• 133373-72-5 6-(4-Chloro-2-fluoro-phenylamino)-3-methyl-1H-pyrimidine-2,4-dione 
• 625-98-9 3-chlorofluorobenzene 
• 305371-34-0 4-(4-chloro-2-fluoro-phenylamino)-6-fluoro-[1.7]naphthyridine-3-carbonitrile 
• 59280-70-5 4'-chloro-2'-fluoroacetanilide 
• 243983-42-8 ethyl 6-[N-(4-chloro-2-fluorophenyl)sulfamoyl]-1-cyclohexene-1-carboxylate 
• 68034-69-5 4-chloro-2-fluoro-phenyl isothiocyanate 
• 205447-81-0 4-(4-chloro-2-fluoroanilino)-7-methoxy-6-methoxycarbonylquinoline 
• 205447-84-3 7-benzyloxy-4-(4-chloro-2-fluoroanilino)-6-cyanoquinoline hydrochloride 
• 205447-78-5 4-(4-chloro-2-fluoroanilino)-6-cyano-7-(2-methoxyethoxy)quinoline hydrochloride 

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.

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Facile synthesis and herbicidal activities of new isoxazole derivatives via 1,3-dipolar cycloaddition reaction

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