5509-65-9

Basic information

• Product Name: 2,6-Difluoroaniline
• Synonyms: Benzenamine, 2,6-difluoro-;2,6-DIFLUOROANILINE;2,6-DIFLUOROBENZENAMINE;2,6-DIFLUOROANILINE, 97+%;2,6-Difluoroaniline,98%;2,6-Difluoroaniline,min.97%;2,6-Difluoroaniline 98%;2,6-Difluoroaniline, min. 97%
• CAS NO: 5509-65-9
• Molecular Formula: C₆H₅F₂N
• Molecular Weight: 129.11
• EINECS: 226-853-0
• Product Categories: Fluorobenzene Series;Anilines, Aromatic Amines and Nitro Compounds;Fluorobenzene;Miscellaneous;Amines;C2 to C6;Nitrogen Compounds
• Mol File: 5509-65-9.mol
• Article Data: 9

Chemical Properties

• Melting Point: 144-148C
• Boiling Point: 51-52 °C15 mm Hg(lit.)
• Flash Point: 110 °F
• Appearance: Clear yellow to brown/Liquid
• Density: 1.199 g/mL at 25 °C(lit.)
• Vapor Pressure: 1.98E-06mmHg at 25°C
• Refractive Index: n20/D 1.508(lit.)
• Storage Temp.: Flammables area
• Solubility: Chloroform, Ethyl Acetate (Slightly)
• PKA: 1.81±0.10(Predicted)
• Water Solubility: Slightly soluble in water.
• Stability: Hygroscopic
• BRN: 2802697
• CAS DataBase Reference: 2,6-Difluoroaniline(CAS DataBase Reference)
• NIST Chemistry Reference: 2,6-Difluoroaniline(5509-65-9)
• EPA Substance Registry System: 2,6-Difluoroaniline(5509-65-9)

Safety Data

• Hazard Codes: Xn,Xi,F
• Statements: 10-20/21/22-36/37/38
• Safety Statements: 36-36/37/39-26-23-16-16/23/26/36/37/39-24/25
• RIDADR: UN 1993 3/PG 3
• WGK Germany: 3
• F: 8-10-23
• HazardClass: 3
• PackingGroup: III
• Hazardous Substances Data: 5509-65-9(Hazardous Substances Data)

Usage

Chemical Properties

clear yellow to brown liquid

Uses

Different sources of media describe the Uses of 5509-65-9 differently. You can refer to the following data:
1. 2,6-Difluoroaniline is an important chemical in the sythesis technology for high-efficiency insecticide.
2. 2,6-Difluoroaniline was used in the synthesis of:N-2,6-difluorophenyl-5-methoxy-1,2,4-triazolo[1,5-a]pyrimidine-2-sulfonamide, herbicidal compoundseries of 2,6,9-trisubstituted purine inhibitors of p38α kinasesubstituted phenylthiomorpholine dioxide, an active pharmaceutical intermediate

InChI:InChI:1S/C6H5F2N/c7-4-2-1-3-5(8)6(4)9/h1-3H,9H2

Synthetic route

2,6-difluorobenzamide (18063-03-1) → 2,6-difluoroaniline (5509-65-9)

Conditions	Yield
With sodium hypochlorite; sodium hydroxide In water at -5℃; for 2h; Reagent/catalyst; Hofmann Rearrangement; Large scale; Green chemistry;	92%
With sodium hypochlorite; sodium hydroxide at -5℃; for 1.5h; Large scale;	89.6%

1-chloro-2,6-difluorobenzene (38361-37-4) → ortho-difluorobenzene (367-11-3) + 2,6-difluoroaniline (5509-65-9)

Conditions	Yield
With ammonium hydroxide; copper(I) oxide at 160℃; for 24h; bomb; Further byproducts given;	A 2% B 71%

2-azido-1,3-difluorobenzene (102284-85-5) + toluene (108-88-3) → 2,6-difluoroaniline (5509-65-9) + N-benzyl-2,6-difluoroaniline + cis-1,2-bis(2,6-difluorophenyl)diazene

Conditions	Yield
With naphtophenone at 25℃; for 4h; Product distribution; Irradiation; further tenmperatures;	A 54% B 13% C 10%

2,6-difluorobenzoic acid (385-00-2) → 2,6-difluoroaniline (5509-65-9)

Conditions	Yield
With sodium azide; sulfuric acid

1-chloro-3,5-difluorobenzene (1435-43-4) → 2,4-difluorophenylamine (367-25-9) + 2,6-difluoroaniline (5509-65-9)

Conditions	Yield
Yield given. Multistep reaction. Yields of byproduct given. Title compound not separated from byproducts;

1,2,3-trichlorobenzene (87-61-6) → 2,3-difluoroanilline (4519-40-8) + 2,6-difluoroaniline (5509-65-9)

Conditions	Yield
With ammonium hydroxide; cesium fluoride; copper(I) oxide 1.) N,N'-dimethylethyleneurea, 250 deg C (bomb), 12 h, 2.) 170 deg C (bomb), 24 h; Yield given. Multistep reaction. Further byproducts given. Yields of byproduct given;
With ammonium hydroxide; cesium fluoride; copper(I) oxide 1.) N,N'-dimethylethyleneurea, 250 deg C (bomb), 12 h, 2.) 160 deg C (bomb), 24 h; Yield given. Multistep reaction. Further byproducts given. Yields of byproduct given;

1,2,3-trichlorobenzene (87-61-6) → 2,6-difluoroaniline (5509-65-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) CsF, 2.) H2, N-ethyldiethanolamine / 2.) 10percent Pd/C / 1.) N,N'-dimethylethyleneurea, 250 deg C (bomb), 12 h, 2.) ethylene glycol, 100 deg C, 200 psi 2: 71 percent / conc. NH4OH / Cu2O / 24 h / 160 °C / bomb View Scheme
Multi-step reaction with 2 steps 1: CsF / various solvent(s) / 12 h / 250 °C / reaction carried out in a bomb 2: 71 percent / conc. NH4OH / Cu2O / 24 h / 160 °C / bomb View Scheme

1,3,5-trichlorobenzene (108-70-3) → 2,6-difluoroaniline (5509-65-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: KF / various solvent(s) / 12 h / 300 °C View Scheme

1,3-Difluorobenzene (372-18-9) → 2,6-difluoroaniline (5509-65-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: (i) nBuLi, (ii) /BRN= 1900390/ 2: NaN3, H2SO4 View Scheme

2-Fluoroaniline (348-54-9) → 2,6-difluoroaniline (5509-65-9)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: copper(I) bromide; pyridine / toluene / 20 h / 60 °C 2.1: potassium nitrate; bis(dibenzylideneacetone)-palladium(0); N-fluorobis(benzenesulfon)imide / ethyl acetate / 12 h / 90 °C / Sealed tube 2.2: 0.17 h / 20 °C View Scheme

aniline (62-53-3) → 2,6-difluoroaniline (5509-65-9)

Conditions

Yield

Multi-step reaction with 4 steps 1.1: copper(I) bromide; pyridine / toluene / 20 h / 60 °C 2.1: potassium nitrate; bis(dibenzylideneacetone)-palladium(0); N-fluorobis(benzenesulfon)imide / ethanol / 12 h / 55 °C / Sealed tube 2.2: 0.17 h / 20 °C 3.1: copper(I) bromide; pyridine / toluene / 20 h / 60 °C 4.1: potassium nitrate; bis(dibenzylideneacetone)-palladium(0); N-fluorobis(benzenesulfon)imide / ethyl acetate / 12 h / 90 °C / Sealed tube 4.2: 0.17 h / 20 °C View Scheme

2,2'-difluoroazobenzene (401-44-5) → 2,6-difluoroaniline (5509-65-9)

Conditions	Yield
Stage #1: 2,2'-difluoroazobenzene With N-fluorobis(benzenesulfon)imide; potassium nitrate; bis(dibenzylideneacetone)-palladium(0) In ethyl acetate at 90℃; for 12h; Sealed tube; Stage #2: With sodium tetrahydroborate; copper(l) chloride In ethanol at 20℃; for 0.166667h;	41.3 mg
Multi-step reaction with 2 steps 1: bis(dibenzylideneacetone)-palladium(0); N-fluorobis(benzenesulfon)imide; potassium nitrate / ethyl acetate / 12 h / 105 °C / Sealed tube 2: sodium tetrahydroborate; copper(l) chloride / ethanol / 20 °C View Scheme

Azobenzene (1227476-15-4) → 2,6-difluoroaniline (5509-65-9)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: potassium nitrate; bis(dibenzylideneacetone)-palladium(0); N-fluorobis(benzenesulfon)imide / ethanol / 12 h / 55 °C / Sealed tube 1.2: 0.17 h / 20 °C 2.1: copper(I) bromide; pyridine / toluene / 20 h / 60 °C 3.1: potassium nitrate; bis(dibenzylideneacetone)-palladium(0); N-fluorobis(benzenesulfon)imide / ethyl acetate / 12 h / 90 °C / Sealed tube 3.2: 0.17 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1: bis(dibenzylideneacetone)-palladium(0); N-fluorobis(benzenesulfon)imide; potassium nitrate / ethyl acetate / 12 h / 55 °C 2: bis(dibenzylideneacetone)-palladium(0); N-fluorobis(benzenesulfon)imide; potassium nitrate / ethyl acetate / 12 h / 105 °C / Sealed tube 3: sodium tetrahydroborate; copper(l) chloride / ethanol / 20 °C View Scheme

C15H14F2N2 → 2,6-difluoroaniline (5509-65-9)

Conditions	Yield
With sodium tetrahydroborate; copper(l) chloride In ethanol at 20℃;	23.2 mg

Pd2(azobenzene)2Cl2 → 2,6-difluoroaniline (5509-65-9)

Conditions	Yield
Multi-step reaction with 4 steps 1: ethyl acetate / 2 h / 20 °C / Sealed tube 2: bis(dibenzylideneacetone)-palladium(0); N-fluorobis(benzenesulfon)imide; potassium nitrate / ethyl acetate / 12 h / 55 °C 3: bis(dibenzylideneacetone)-palladium(0); N-fluorobis(benzenesulfon)imide; potassium nitrate / ethyl acetate / 12 h / 105 °C / Sealed tube 4: sodium tetrahydroborate; copper(l) chloride / ethanol / 20 °C View Scheme
Multi-step reaction with 4 steps 1: N-fluorobis(benzenesulfon)imide / ethyl acetate / 2 h / 20 °C / Sealed tube 2: bis(dibenzylideneacetone)-palladium(0); N-fluorobis(benzenesulfon)imide; potassium nitrate / ethyl acetate / 12 h / 55 °C 3: bis(dibenzylideneacetone)-palladium(0); N-fluorobis(benzenesulfon)imide; potassium nitrate / ethyl acetate / 12 h / 105 °C / Sealed tube 4: sodium tetrahydroborate; copper(l) chloride / ethanol / 20 °C View Scheme
Multi-step reaction with 5 steps 1: dichloromethane / 24 h / 20 °C 2: ethyl acetate / 2 h / 20 °C / Sealed tube 3: bis(dibenzylideneacetone)-palladium(0); N-fluorobis(benzenesulfon)imide; potassium nitrate / ethyl acetate / 12 h / 55 °C 4: bis(dibenzylideneacetone)-palladium(0); N-fluorobis(benzenesulfon)imide; potassium nitrate / ethyl acetate / 12 h / 105 °C / Sealed tube 5: sodium tetrahydroborate; copper(l) chloride / ethanol / 20 °C View Scheme

C14H12N4O2Pd → 2,6-difluoroaniline (5509-65-9)

Conditions

Yield

Multi-step reaction with 4 steps 1: ethyl acetate / 2 h / 20 °C / Sealed tube 2: bis(dibenzylideneacetone)-palladium(0); N-fluorobis(benzenesulfon)imide; potassium nitrate / ethyl acetate / 12 h / 55 °C 3: bis(dibenzylideneacetone)-palladium(0); N-fluorobis(benzenesulfon)imide; potassium nitrate / ethyl acetate / 12 h / 105 °C / Sealed tube 4: sodium tetrahydroborate; copper(l) chloride / ethanol / 20 °C View Scheme

1-(2,4,6-trimethylphenyl)-2-phenyldiazene (20488-57-7, 20488-58-8, 29418-26-6) → 2,6-difluoroaniline (5509-65-9)

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

2,2',6-trifluoroazobenzene → 2,6-difluoroaniline (5509-65-9)

Conditions	Yield
With sodium tetrahydroborate; copper(l) chloride In ethanol at 20℃;	24.8 mg

2,6-difluoroaniline (5509-65-9) → 1,3-difluoro-2-nitrosobenzene (29270-54-0)

Conditions	Yield
With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 0 - 23℃; Inert atmosphere;	100%
With Oxone In dichloromethane; water at 20℃; for 15h;	99%
With potassium peroxymonosulfate sulfate In dichloromethane; water at 20℃; for 24h;	86.49%

2,6-difluoroaniline (5509-65-9) → 2,6-difluoro-4-iodoaniline (141743-49-9)

Conditions	Yield
With N-iodo-succinimide; toluene-4-sulfonic acid In N,N-dimethyl-formamide at 5 - 20℃; for 2.5h;	100%
With Iodine monochloride In acetic acid at 20℃; for 0.25h;	95%
Stage #1: 2,6-difluoroaniline With Iodine monochloride; acetic acid In water at 20℃; for 0.25h; Stage #2: With sodium carbonate In water	95%

2,6-difluoroaniline (5509-65-9) + Ethyl oxalyl chloride (4755-77-5) → ethyl 2-((2,6-difluorophenyl)amino)-2-oxoacetate (648408-62-2)

Conditions	Yield
With triethylamine In tetrahydrofuran at 0 - 20℃; for 24h;	100%
With triethylamine In tetrahydrofuran at 0℃; for 16h; Inert atmosphere;

thiophosgene (463-71-8) + 2,6-difluoroaniline (5509-65-9) → 2,6-difluorophenylisothiocyanate (207974-17-2)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 1h;	99%
With hydrogenchloride In dichloromethane for 3h; Ambient temperature;	78%
In hydrogenchloride; dichloromethane

2,6-difluoroaniline (5509-65-9) → 4-bromo-2,6-difluoroaniline (67567-26-4)

Conditions	Yield
With N-Bromosuccinimide In acetonitrile at 20℃;	99%
With N-Bromosuccinimide In chloroform at 20℃;	93%
Stage #1: 2,6-difluoroaniline With bromine; acetic acid In water at 20℃; for 0.25h; Stage #2: With sodium carbonate In water	92%

2,6-difluoroaniline (5509-65-9) + acetic anhydride (108-24-7) → N-(2,6-difluorophenyl)acetamide (3896-29-5)

Conditions	Yield
In dichloromethane at 20℃; for 16h;	98%
In toluene at 0 - 20℃; for 4h; Solvent; Temperature;	94%
	91%

3,5-diodosalicylaldehyde (2631-77-8) + 2,6-difluoroaniline (5509-65-9) → N-(3',5'-diiodo-salycilidene)-2,6-difluoroaniline

Conditions	Yield
With trifluoroacetic acid In toluene at 120℃; for 16h;	98%

2,6-difluoroaniline (5509-65-9) + potassium ethyl xanthogenate (140-89-6) → 2-mercapto-4-fluorobenzothiazole (154327-24-9)

Conditions	Yield
In N,N-dimethyl-formamide at 120℃; for 0.133333h; microwave irradiation;	98%
In N,N-dimethyl-formamide at 120℃; for 3.5h; Inert atmosphere;	98%
In N,N-dimethyl-formamide at 120℃; for 3.5h; Inert atmosphere;	98%
In 1-methyl-pyrrolidin-2-one at 90℃; for 2h;	56%
In N,N-dimethyl-formamide at 120℃; for 4h;

methyl 3-(3-{2-[(3-{[2-(dimethylamino)ethyl]oxy}-2-methylphenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)benzoate (1089278-91-0) + 2,6-difluoroaniline (5509-65-9) → N-(2,6-difluorophenyl)-3-(3-{2-[(3-{[2-(dimethylamino)ethyl]oxy}-2-methylphenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)benzamide (1089278-89-6)

Conditions	Yield
Stage #1: methyl 3-(3-{2-[(3-{[2-(dimethylamino)ethyl]oxy}-2-methylphenyl)amino}-4-pyrimidinyl]imidazo[1,2-a]pyridin-2-yl)benzoate; 2,6-difluoroaniline With sodium hexamethyldisilazane In tetrahydrofuran at 20℃; for 0.0833333h; Stage #2: With sodium hydrogencarbonate In tetrahydrofuran; water	98%

4-iodoanisol (529-28-2) + 2,6-difluoroaniline (5509-65-9) → 2,6-difluoro-N-(2-methoxyphenyl)aniline

Conditions	Yield
With tris(dibenzylideneacetone)dipalladium(0) chloroform complex; tri-tert-butyl phosphine; sodium t-butanolate In toluene at 100℃; Buchwald-Hartwig Coupling; Inert atmosphere;	98%
With tris(dibenzylideneacetone)dipalladium(0) chloroform complex; tri-tert-butyl phosphine; sodium t-butanolate In toluene at 100℃; for 16h; Buchwald-Hartwig Coupling; Inert atmosphere;	96%
With tris(dibenzylideneacetone)dipalladium(0) chloroform complex; tri-tert-butyl phosphine In toluene at 100℃; Inert atmosphere;

2,6-difluoroaniline (5509-65-9) + acetylacetone (123-54-6) → 3-(2-(2,6-difluorophenyl)hydrazono)pentane-2,4-dione

Conditions	Yield
Stage #1: 2,6-difluoroaniline With hydrogenchloride; sodium nitrite In water at 0 - 5℃; for 0.5h; Stage #2: acetylacetone With sodium acetate In methanol; water at 20℃;	98%
Stage #1: 2,6-difluoroaniline With hydrogenchloride; acetic acid; sodium nitrite In water at 0℃; for 0.75h; Stage #2: acetylacetone With sodium acetate In ethanol; water for 1h;	94%

2,6-difluoroaniline (5509-65-9) + acetylacetone (123-54-6) → C11H10F2N2O2

Conditions	Yield
Stage #1: 2,6-difluoroaniline With hydrogenchloride; sodium nitrite In water at 0 - 5℃; for 0.5h; Stage #2: acetylacetone With sodium acetate In ethanol; water at 0 - 20℃; for 10h;	98%

2,6-difluoroaniline (5509-65-9) + 2-nitrobenzyl chloride (610-14-0) → N-(2,6-difluorophenyl)-2-nitrobenzamide (936025-10-4)

Conditions	Yield
In 1,4-dioxane at 20℃;	97%

2,6-difluoroaniline (5509-65-9) + 4,4,5,5-tetramethyl-[1,3,2]-dioxaboralane (25015-63-8) → C12H16BF2NO2

Conditions	Yield
In [D3]acetonitrile at 20℃; for 6h; Inert atmosphere;	97%

2,6-difluoroaniline (5509-65-9) + acetaldehyde (75-07-0) → N-ethyl-2,6-difluoroaniline (13800-03-8)

Conditions	Yield
Stage #1: acetaldehyde With sodium tetrahydroborate; acetic acid In 1,2-dichloro-ethane at 0 - 20℃; for 1h; Stage #2: 2,6-difluoroaniline In 1,2-dichloro-ethane at 20℃;	97%

2-bromothiazole-4-carboxylic Acid (5198-88-9) + 2,6-difluoroaniline (5509-65-9) → 2-bromo-N-(2,6-difluorophenyl)thiazole-4-carboxamide

Conditions	Yield
Stage #1: 2-bromothiazole-4-carboxylic Acid With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 20℃; for 0.25h; Stage #2: 2,6-difluoroaniline In N,N-dimethyl-formamide at 20℃; for 16h;	96%

2,6-difluoroaniline (5509-65-9) + 4-bromo-5-fluoro-2-{[(2S)-1,1,1-trifluoropropan-2-yl]oxy}benzoyl chloride → 4-bromo-N-(2,6-difluorophenyl)-5-fluoro-2-{[(2S)-1,1,1-trifluoropropan-2-yl]oxy}benzamide

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 1h; Inert atmosphere;	96%
With triethylamine In dichloromethane at 20℃; for 1h;	96%

2,6-difluoroaniline (5509-65-9) + 2-(4-bromophenyl)benzothiazole (19654-19-4) → N-(4-(benzo[d]thiazol-2-yl)phenyl)-2,6-difluoroaniline

Conditions	Yield
With C47H70BrO4PPdSi; sodium t-butanolate In tetrahydrofuran at 20℃; for 1h; Reagent/catalyst; Solvent; Schlenk technique; Inert atmosphere; Sealed tube;	96%

2,6-difluoroaniline (5509-65-9) + 2-(bromomethyl)benzonitrile (22115-41-9) → 2-(2,6-difluorophenyl)-2,3-dihydro-isoindol-1-ylideneamine hydrobromide

Conditions	Yield
at 150℃; for 16h; Schlenk technique; Inert atmosphere;	95.3%

2,6-difluoroaniline (5509-65-9) + pivaloyl chloride (3282-30-2) → N-(2,6-difluorophenyl)trimethylacetamide (1240020-41-0)

Conditions	Yield
With triethylamine In toluene at 0 - 50℃;	95%
In toluene at 20℃; Reflux;

2-chlorosulfonyl-8-fluoro-5-methoxy-[1,2,4]triazolo[1,5-c]pyrimidine (147150-78-5) + 2,6-difluoroaniline (5509-65-9) → florasulam (145701-23-1)

Conditions	Yield
Stage #1: 2,6-difluoroaniline With N-chloro-succinimide; dimethylsulfide In acetonitrile at -20℃; Inert atmosphere; Stage #2: 2-chlorosulfonyl-8-fluoro-5-methoxy-[1,2,4]triazolo[1,5-c]pyrimidine With 3-Methylpyridine In acetonitrile at 20 - 40℃; Temperature; Inert atmosphere;	94.2%
In propylene glycol at 40℃; for 1.5h; Product distribution / selectivity;	88%
In propylene glycol; dichloromethane at 25 - 45℃; for 5.5 - 8h; Product distribution / selectivity;	84.6%

2,6-difluoroaniline (5509-65-9) → N-sulfinyl-2,6-diflouroaniline (80829-40-9)

Conditions	Yield
With N-(chlorosulfinyl)imidazole In dichloromethane at -40 - 20℃; for 1.5h; Inert atmosphere;	94%
With thionyl chloride

4-methoxypyridine (620-08-6) + 2,6-difluoroaniline (5509-65-9) → N-(2,6-difluorophenyl)pyridin-4-amine

Conditions	Yield
With potassium hexamethylsilazane In tetrahydrofuran at 100℃; for 16h; Inert atmosphere; Schlenk technique; Sealed tube; Green chemistry;	94%

2,6-difluoroaniline (5509-65-9) + 4-acetophenyl triflate (109613-00-5) → 1-(4-((2,6-difluorophenyl)amino)phenyl)ethan-1-one

Conditions	Yield
With C46H27F24FeNiP2(1+)*CF3O3S(1-); triethylamine In 2-methyltetrahydrofuran at 100℃; for 16h; Concentration; Schlenk technique; Inert atmosphere; Glovebox; Sealed tube;	94%

o-benzenedisulfonimide (4482-01-3) + 2,6-difluoroaniline (5509-65-9) → 2,6-difluorobenzenediazonium o-benzenedisulfonimide

Conditions	Yield
With acetic acid; isopentyl nitrite at 0 - 5℃; Diazotization;	93%

2,6-difluoroaniline (5509-65-9) + ortho-nitrofluorobenzene (1493-27-2) → 2,6-difluoro-N-(2-nitrophenyl)aniline (1033225-43-2)

Conditions	Yield
Stage #1: 2,6-difluoroaniline With sodium tert-amylate In tetrahydrofuran at 0 - 10℃; for 1.11667h; Large scale reaction; Stage #2: ortho-nitrofluorobenzene In tetrahydrofuran at 9 - 15℃; for 3h; Thermodynamic data; Concentration; Time; Large scale reaction;	93%
Stage #1: 2,6-difluoroaniline With tert.-butyl lithium In tetrahydrofuran; pentane at -78℃; for 0.166667h; Stage #2: ortho-nitrofluorobenzene In tetrahydrofuran; pentane at 0 - 20℃; for 0.5h;	68%
Stage #1: 2,6-difluoroaniline With sodium hydride In N,N-dimethyl-formamide for 0.5h; Stage #2: ortho-nitrofluorobenzene In N,N-dimethyl-formamide for 16h;

2-chloro-7-(1-methyl-1H-pyrazol-4-yl)-1,5-naphthyridine (1422126-58-6) + 2,6-difluoroaniline (5509-65-9) → C18H13F2N5 (1431985-43-1)

Conditions	Yield
Stage #1: 2,6-difluoroaniline With lithium hexamethyldisilazane In tetrahydrofuran at 0℃; for 1h; Stage #2: 2-chloro-7-(1-methyl-1H-pyrazol-4-yl)-1,5-naphthyridine In tetrahydrofuran at 0 - 20℃;	93%

1,3-diphenyl-3-hydroxypropene (4663-33-6, 62668-02-4, 62839-70-7, 116127-91-4, 132014-29-0, 136981-81-2, 148616-45-9) + 2,6-difluoroaniline (5509-65-9) → C21H17F2N

Conditions	Yield
With copper(II) bis(trifluoromethanesulfonate) In 1,2-dichloro-ethane at 70℃; for 3h; regioselective reaction;	93%

2,6-difluoroaniline (5509-65-9) + 4-bromo-2,6-difluoroaniline (67567-26-4) → (E)-1-(4-bromo-2,6-difluorophenyl)-2-(2,6-difluorophenyl)diazene

Conditions	Yield
Stage #1: 2,6-difluoroaniline; 4-bromo-2,6-difluoroaniline With Oxone In dichloromethane; water at 20℃; for 17h; Inert atmosphere; Stage #2: In acetic acid; toluene; trifluoroacetic acid at 20℃;	93%

2,6-difluoroaniline (5509-65-9) + acetyl chloride (75-36-5) → N-(2,6-difluorophenyl)acetamide (3896-29-5)

Conditions	Yield
In toluene at 0 - 20℃; for 4h;	93%

Upstream product

• 385-00-2 2,6-difluorobenzoic acid 
• 1435-43-4 1-chloro-3,5-difluorobenzene 
• 38361-37-4 1-chloro-2,6-difluorobenzene 
• 20488-57-7 1-(2,4,6-trimethylphenyl)-2-phenyldiazene 
• 1227476-15-4 Azobenzene 
• 401-44-5 2,2'-difluoroazobenzene 
• 62-53-3 aniline 
• 348-54-9 2-Fluoroaniline 
• 18063-03-1 2,6-difluorobenzamide 
• 372-18-9 1,3-Difluorobenzene 
• 108-70-3 1,3,5-trichlorobenzene 
• 87-61-6 1,2,3-trichlorobenzene 
• 102284-85-5 2-azido-1,3-difluorobenzene 
• 108-88-3 toluene 

Downstream Products

• 98500-60-8 N-(2,6-difluoro-phenyl)-oxalamic acid methyl ester 
• 154327-24-9 4-fluoro-2-mercaptobenzothiazole 
• 909487-06-5 1,3-bis-(2,6-difluoro-phenyl)-4,5-dihydro-3H-imidazol-1-ium; chloride 
• 873943-92-1 N-(2,6-difluoro-phenyl)-N'-(4-hydroxy-6-methyl-pyrimidin-2-yl)-guanidine 
• 694504-20-6 2,6-difluoro-[bis(2-hydroxyethyl)]aniline 
• 383199-89-1 4-(2,6-difluorophenyl)thiomorpholine 1,1-dioxide 

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.

A aqueous phase preparation 2, 6 - [...] method

The invention relates to a green preparation 2, 6 - [...] synthetic method, to industrial product is 2, 6 - difluoro-benzamide as the starting material, passes through the aqueous phase Huffman degradation reaction, the aqueous phase diazotisations directly after the hydrolysis, direct concentrated nitric acid nitration, the iron powder reduces the aqueous phase, the aqueous phase with the aqueous phase to diazotization coupling reaction of phenol, after five step process for preparing aqueous phase reactions 2, 6 - [...] production process and corresponding various process conditions. The beneficial effect of the present invention is: select industrialized product 2, 6 - difluoro-benzamide as the raw material, raw materials are easy, low cost, through the aqueous phase reaction and solvent-free reaction for the preparation of 2, 6 - [...], its mild reaction conditions and environmental, safety and high efficiency. The present invention provides a kind of environmental protection, model, high efficiency can be used for the industrial production of 2, 6 - [...] green synthetic pathway.

AROMATIC FLUORINE CHEMISTRY. PART 4. PREPARATION OF 2,6-DIFLUOROANILINE

The preparation of 2,6-difluoroaniline from 1,3,5-trichlorobenzene is described. 1-Chloro-3,5-difluorobenzene prepared via KF exchange on 1,3,5-trichlorobenzene is dichlorinated and nitrated in a single reactor to a mixture of trichlorodifluoronitrobenzenes.The latter are reduced to ca. 4:1 mixture of 2,6-difluoroaniline and 2,4-difluoroaniline.