3863-11-4

Basic information

• Product Name: 3,4-Difluoroaniline
• Synonyms: 3,4-Difluoroaniline, 99+% 2.5ML;3,4-Difluoroaniline 98%, 4-Difluoroaniline 98%;3, 4-2 fluoro aniline;TIMTEC-BB SBB007915;3,4-DIFLUOROANILINE;3,4-DIFLUOROBENZENAMINE;AKOS 91142;3,4-difluoro-benzenamin
• CAS NO: 3863-11-4
• Molecular Formula: C₆H₅F₂N
• Molecular Weight: 129.11
• EINECS: 223-381-7
• Product Categories: Nitrogen Compounds;Fluorine series;Fluorobenzene Series;Anilines, Aromatic Amines and Nitro Compounds;Anilines, Amides & Amines;Fluorine Compounds;Amines;C2 to C6
• Mol File: 3863-11-4.mol
• Article Data: 20

Chemical Properties

• Melting Point: 22°C
• Boiling Point: 77 °C7 mm Hg(lit.)
• Flash Point: 185 °F
• Appearance: clear yellow to straw liquid after melting
• Density: 1.302 g/mL at 25 °C(lit.)
• Vapor Pressure: 18.1mmHg at 25°C
• Refractive Index: n20/D 1.513(lit.)
• Storage Temp.: Keep in dark place,Inert atmosphere,Room temperature
• PKA: 3?+-.0.10(Predicted)
• Water Solubility: SLIGHTLY SOLUBLE
• BRN: 971235
• CAS DataBase Reference: 3,4-Difluoroaniline(CAS DataBase Reference)
• NIST Chemistry Reference: 3,4-Difluoroaniline(3863-11-4)
• EPA Substance Registry System: 3,4-Difluoroaniline(3863-11-4)

Safety Data

• Hazard Codes: Xn,Xi
• Statements: 22-36/37/38-20/21/22
• Safety Statements: 26-36-36/37/39
• RIDADR: UN 2941 6.1/PG 3
• WGK Germany: 3
• RTECS: CX9871900
• F: 8-10-23
• HazardClass: 6.1
• PackingGroup: III
• Hazardous Substances Data: 3863-11-4(Hazardous Substances Data)

Usage

Chemical Properties

clear yellow to straw liquid after melting

Uses

3,4-Difluoroaniline was used in the synthesis of (3,4-disfluoro)phenylquione.

General Description

3,4-Difluoroaniline (3,4-DFA) was degraded, under aerobic conditions, by Pseudomonas fluorescens.

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

Synthetic route

1-tert-butyl-N-(3,4-difluorophenyl)-1,1-dimethylsilanamine (1321455-41-7) → 3,4-difluoroaniline (3863-11-4)

Conditions	Yield
With silica gel In ethanol; water at 20℃; for 2h;	100%

3,4-difluoronitrobenzene (369-34-6) → 3,4-difluoroaniline (3863-11-4)

Conditions	Yield
With sodium tetrahydroborate; water at 0 - 20℃; for 4h;	95%
With palladium on activated charcoal; hydrogen In toluene at 25 - 35℃; under 1500.15 - 4500.45 Torr; Autoclave;	93.8%
With cyclohexa-1,4-diene; 5%-palladium/activated carbon In methanol at 120℃; for 0.0833333h; Microwave irradiation;	82%

3,4-difluoronitrobenzene (369-34-6) + iron (7439-89-6) → 3,4-difluoroaniline (3863-11-4)

Conditions	Yield
With hydrogenchloride In methanol	86%

(3,4-difluoro-phenyl)-carbamic acid benzyl ester (250372-11-3) → 3,4-difluoroaniline (3863-11-4)

Conditions	Yield
With methanol; sodium tetrahydroborate; nickel(II) chloride hexahydrate at 20℃; for 0.25h; chemoselective reaction;	83%

(3,4-difluoro-phenyl)-amide (85118-04-3) → 3,4-difluoroaniline (3863-11-4)

Conditions	Yield
With potassium hydroxide; bromine In water at 0 - 88℃; for 1h;	65%

4-fluoroaniline (371-40-4) → 2,4-difluorophenylamine (367-25-9) + 3,4-difluoroaniline (3863-11-4)

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

aniline (62-53-3) + α-chloro-propionic acid amide → 3,4-difluoroaniline (3863-11-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: F2; TfOH / 20 °C 2: F2; TfOH / 20 °C View Scheme

ortho-difluorobenzene (367-11-3) → 3,4-difluoroaniline (3863-11-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: HNO3, H2SO4 2: Fe, HCl View Scheme

4-chlorotrichloromethylbenzene (5216-25-1) → 3,4-difluoroaniline (3863-11-4)

Conditions	Yield
Multi-step reaction with 6 steps 1: chlorosulfuric acid / 1) 120 deg C, 1 h 2) 150 deg C, 2 h 2: 94 percent / SOCl2 / benzene / 8 h / Heating 3: 71 percent / KF, Ph4PBr / acetonitrile / 16 h / Heating 4: 45 percent / KF, PPh4Br / tetrahydrothiophene 1,1-dioxide; toluene / 210 °C / 270 Torr 5: 82 percent / 25 aq. NH3 / H2O / 2 h 6: 65 percent / Br2, aq. KOH / H2O / 1 h / 0 - 88 °C View Scheme

4-chloro-3-(chlorosulfonyl)benzoic acid (2494-79-3) → 3,4-difluoroaniline (3863-11-4)

Conditions	Yield
Multi-step reaction with 5 steps 1: 94 percent / SOCl2 / benzene / 8 h / Heating 2: 71 percent / KF, Ph4PBr / acetonitrile / 16 h / Heating 3: 45 percent / KF, PPh4Br / tetrahydrothiophene 1,1-dioxide; toluene / 210 °C / 270 Torr 4: 82 percent / 25 aq. NH3 / H2O / 2 h 5: 65 percent / Br2, aq. KOH / H2O / 1 h / 0 - 88 °C View Scheme

3-chlorosulfonyl-4-chlorobenzoyl chloride (62574-66-7) → 3,4-difluoroaniline (3863-11-4)

Conditions	Yield
Multi-step reaction with 4 steps 1: 71 percent / KF, Ph4PBr / acetonitrile / 16 h / Heating 2: 45 percent / KF, PPh4Br / tetrahydrothiophene 1,1-dioxide; toluene / 210 °C / 270 Torr 3: 82 percent / 25 aq. NH3 / H2O / 2 h 4: 65 percent / Br2, aq. KOH / H2O / 1 h / 0 - 88 °C View Scheme

3,4-difluorobenzoyl fluoride (127269-25-4) → 3,4-difluoroaniline (3863-11-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 82 percent / 25 aq. NH3 / H2O / 2 h 2: 65 percent / Br2, aq. KOH / H2O / 1 h / 0 - 88 °C View Scheme

4-fluoro-3-(fluorosulfonyl)benzoyl fluoride (127986-80-5) → 3,4-difluoroaniline (3863-11-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: 45 percent / KF, PPh4Br / tetrahydrothiophene 1,1-dioxide; toluene / 210 °C / 270 Torr 2: 82 percent / 25 aq. NH3 / H2O / 2 h 3: 65 percent / Br2, aq. KOH / H2O / 1 h / 0 - 88 °C View Scheme

Methyl formate (107-31-3) + 3,4-difluoroaniline (3863-11-4) → 3,4-di-fluorophenyl formamide (138563-55-0)

Conditions	Yield
With sodium hexamethyldisilazane In tetrahydrofuran at 0 - 20℃;	100%

2-Amino-6-chloropurin (10310-21-1) + 3,4-difluoroaniline (3863-11-4) → N6-(3,4-difluorophenyl)-9H-purine-2,6-diamine

Conditions	Yield
at 130℃; for 0.0833333h; Irradiation;	100%

ethyl 3-fluoro-4-((2-(hydroxymethyl)azetidin-1-yl)sulfonyl)-1-methyl-1H-pyrrole-2-carboxylate + 3,4-difluoroaniline (3863-11-4) → N-(3,4-difluorophenyl)-3-fluoro-4-((2-(hydroxymethyl)azetidin-1-yl)sulfonyl)-1-methyl-1H-pyrrole-2-carboxamide

Conditions	Yield
With ammonium chloride; lithium hexamethyldisilazane In tetrahydrofuran; dichloromethane at 20℃;	100%

acetic anhydride (108-24-7) + 3,4-difluoroaniline (3863-11-4) → 3,4-difluoroacetanilide (458-11-7)

Conditions	Yield
In 1,4-dioxane at 0℃; for 1h; Inert atmosphere; Schlenk technique;	99%
at 20℃; for 0.5h;	95%
With triethylamine In dichloromethane at 20℃; for 1h;	91%

dimethyl acetylenedicarboxylate (762-42-5) + 3,4-difluoroaniline (3863-11-4) → methyl 3-carbomethoxy-3-(3',4'-difluorophenyl)amino-2-propenoate (251986-50-2)

Conditions	Yield
In methanol at 20℃; Addition;	99%

pivaloyl chloride (3282-30-2) + 3,4-difluoroaniline (3863-11-4) → N-pivaloyl-3,4-difluoroaniline (205756-46-3)

Conditions	Yield
With triethylamine at 0 - 20℃; for 1h;	99%
With triethylamine In benzene at 0℃;	98%
With TEA In dichloromethane at 0 - 25℃; for 3h; Acylation;
With triethylamine In dichloromethane at 0 - 20℃; for 1h;
With triethylamine In toluene at 20℃;

2-chloropropionyl chloride (7623-09-8) + 3,4-difluoroaniline (3863-11-4) → 2-chloro-N-(3,4-difluoro-phenyl)-propionamide (868771-20-4)

Conditions	Yield
In toluene at 120℃; for 1h;	99%
In toluene Heating;

ethyl (E)-3-(dimethylamino)acrylate (1117-37-9) + 3,4-difluoroaniline (3863-11-4) → ethyl 2-[2-(3,4-difluorophenyl)hydrazinylidene]-3-oxopropanoate

Conditions	Yield
Stage #1: 3,4-difluoroaniline With hydrogenchloride; sodium nitrite In water at 0℃; for 0.0833333h; Stage #2: ethyl (E)-3-(dimethylamino)acrylate With potassium acetate In ethanol; water at 0 - 20℃; for 14h;	99%

2-chloro-5-methoxyquinoline (160893-07-2) + 3,4-difluoroaniline (3863-11-4) → N-(3,4-difluorophenyl)-5-methoxyquinolin-2-amine

Conditions	Yield
In neat (no solvent) at 160℃;	98%
In neat (no solvent) at 160℃;

1,2,3,4-tetrahydroisoquinoline (91-21-4) + 3,4-difluoroaniline (3863-11-4) → C15H15FN2

Conditions	Yield
With silver(I) hexafluorophosphate; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; C17H21O3P In tetrahydrofuran at 120℃; for 20h; Inert atmosphere; Molecular sieve;	98%

hexamethylene imine (111-49-9) + 3,4-difluoroaniline (3863-11-4) → C12H17FN2

Conditions	Yield
With silver(I) hexafluorophosphate; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; C17H21O3P In tetrahydrofuran at 120℃; for 20h; Inert atmosphere; Molecular sieve;	98%
With C17H21O3P; [Ru(cymene)]PF6 In tetrahydrofuran at 120℃; Molecular sieve;	98%

5-(2-bromo-ethyl)-phenanthridinium bromide + 3,4-difluoroaniline (3863-11-4) → 1-(3,4-difluorophenyl)-1,2,3,12b-tetrahydroimidazo[1,2-f]phenanthridine (1192571-37-1)

Conditions	Yield
With triethylamine In chloroform Inert atmosphere;	97.9%

di-tert-butyl dicarbonate (24424-99-5) + 3,4-difluoroaniline (3863-11-4) → (3,4-difluorophenyl)-carbamic acid-tert-butyl ester (144298-04-4)

Conditions	Yield
In tetrahydrofuran at 60℃; for 15h;	97%
In tetrahydrofuran at 20℃; for 12h;	93%
In tetrahydrofuran at 70℃; for 96h;	91%
In tetrahydrofuran at 20℃; for 12h;	65%
In tetrahydrofuran at 60℃; for 16h;

3,4-difluoroaniline (3863-11-4) → 2-iodo-4,5-difluoroaniline (847685-01-2)

Conditions	Yield
With iodine; sodium hydrogencarbonate In water at 20℃; for 0.5h;	97%
With Iodine monochloride In acetic acid at 20℃; for 0.5h;	96%
With iodine; sodium hydrogencarbonate In water at 20℃; for 0.5h;	92%

4-chloro-3-formylcoumarin (50329-91-4) + 3,4-difluoroaniline (3863-11-4) → 6,7-difluoro-4-(2-hydroxyphenyl)quinoline-3-carboxylic acid (1394232-16-6)

Conditions	Yield
With sulfuric acid In methanol at 20℃; for 0.25h;	97%

nitromethane (75-52-5) + methyl 2-butoxy-6-methyl-3,4-dihydro-2H-pyran-5-carboxylate (1266617-35-9) + 3,4-difluoroaniline (3863-11-4) → methyl 1-(3,4-difluorophenyl)-2-methyl-6-(nitromethyl)-1,4,5,6-tetrahydropyridine-3-carboxylate

Conditions	Yield
With lithium bromide monohydrate at 100℃; for 11h;	97%

1-Nitronaphthalene (86-57-7) + 3,4-difluoroaniline (3863-11-4) → C16H11F2N

Conditions	Yield
With bis(acetylacetonato)palladium(II); potassium phosphate tribasic trihydrate; 2-(2,6-diethyl-4-methylphenyl)-5-(2,4,6-triisopropylphenyl)imidazo[1,5-a]pyridin-2-ium chloride In 1,4-dioxane at 130℃; for 24h; Inert atmosphere;	97%

4-(2,6-dichloropyrido[3,4-d]pyrimidin-4-yl)morpholine + 3,4-difluoroaniline (3863-11-4) → 6-chloro-N-(3,4-difluorophenyl)-4-morpholinopyrido[3,4-d]pyrimidin-2-amine

Conditions	Yield
With toluene-4-sulfonic acid In iso-butanol Reflux; Inert atmosphere;	96.4%

3,4-difluoroaniline (3863-11-4) → 4-azido-1,2-difluorobenzene (123330-51-8)

Conditions	Yield
Stage #1: 3,4-difluoroaniline With hydrogenchloride; sodium nitrite In water at 0℃; for 0.5h; Stage #2: With sodium azide In water at 0℃; for 1h;	96.1%
Stage #1: 3,4-difluoroaniline With hydrogenchloride; sodium nitrite In water at 0℃; Stage #2: With sodium azide In water at 0℃;	96.1%
With sodium azide; sulfuric acid; trifluoroacetic acid; sodium nitrite 1.) H2O, RT, 30 min, 2.) 1 h; Yield given. Multistep reaction;

4-chloro-3-formylcoumarin (50329-91-4) + 3,4-difluoroaniline (3863-11-4) → 9,10-difluoro-6H-chromeno[4,3-b]quinolin-6-one (1357063-67-2)

Conditions	Yield
In ethanol at 20℃; for 0.25h; ultrasound irradiation;	96%
In methanol at 20℃; for 0.133333h; ultrasound irradiation;	90%
With Amberlyst-15 In ethanol for 2h; Reflux; Inert atmosphere;	81%

3,4-difluoroaniline (3863-11-4) + 1-(2-methylphenyl)-1,4-pentanedione (195137-30-5) → 1-(3,4-difluorophenyl)-2-methyl-5-(2-methylphenyl)pyrrole (1445874-27-0)

Conditions	Yield
With gadolinium(III) trifluoromethanesulfonate In acetonitrile at 30℃; for 0.5h; Paal-Knorr Pyrrole Synthesis;	96%

ethyl acrylate (140-88-5) + 3,4-difluoroaniline (3863-11-4) → ethyl 3-((3,4-difluorophenyl)amino)propanoate

Conditions	Yield
With trifluorormethanesulfonic acid In neat (no solvent) at 100℃; for 24h;	96%
With trifluorormethanesulfonic acid at 100℃;
With trifluorormethanesulfonic acid at 100℃; for 16h; Inert atmosphere;

Propiolic acid (471-25-0) + 3,4-difluoroaniline (3863-11-4) → N-(3,4-difluorophenyl)prop-2-ynamide

Conditions	Yield
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 5℃; for 1h;	96%

sodium dicyanamide (1934-75-4) + 3,4-difluoroaniline (3863-11-4) → 1-(3,4-difluoro)phenyl-3-cyanoguanidine

Conditions	Yield
With hydrogenchloride In water at 80℃; for 1h;	95.2%
With hydrogenchloride In water at 80℃; for 1h;	95.2%

chloroformic acid ethyl ester (541-41-3) + 3,4-difluoroaniline (3863-11-4) → (3,4-difluorophenyl)carbamic acid ethyl ester (2145-85-9)

Conditions	Yield
With pyridine In tetrahydrofuran at 20℃; for 0.5h;	95%
With sodium carbonate

carbon disulfide (75-15-0) + triethylamine (121-44-8) + 3,4-difluoroaniline (3863-11-4) → 3,4-difluorophenyl dithiocarbamic acid triethylammonium (144514-15-8)

Conditions	Yield
at 0℃;	95%
at 0℃;
In toluene at 25 - 30℃; for 12h; Product distribution / selectivity; Cooling with ice;

3,4-difluoroaniline (3863-11-4) → 3,3',4,4'-tetrafluoroazobenzene

Conditions	Yield
With copper-manganese spinel oxide In ethyl acetate at 80℃; for 8h;	95%
With potassium hydroxide; potassium hexacyanoferrate(III) In ethanol; water for 8h; Heating;	65%
With potassium hydroxide; potassium hexacyanoferrate(III) In ethanol; water for 6h; Heating;	60%

2-chloropropionyl chloride (625-36-5) + 3,4-difluoroaniline (3863-11-4) → 3-chloro-N-(3,4-difluoro-phenyl)-propionamide (132669-28-4)

Conditions	Yield
With pyridine In acetone at 55℃; for 3h;	95%
With triethylamine In ethyl acetate at 20 - 30℃;	73%
With triethylamine In ethyl acetate at 20 - 30℃;

Upstream product

• 369-34-6 3,4-difluoronitrobenzene 
• 7439-89-6 iron 
• 250372-11-3 (3,4-difluoro-phenyl)-carbamic acid benzyl ester 
• 1321455-41-7 1-tert-butyl-N-(3,4-difluorophenyl)-1,1-dimethylsilanamine 
• 127986-80-5 4-fluoro-3-(fluorosulfonyl)benzoyl fluoride 
• 127269-25-4 3,4-difluorobenzoyl fluoride 
• 62574-66-7 3-chlorosulfonyl-4-chlorobenzoyl chloride 
• 2494-79-3 4-chloro-3-(chlorosulfonyl)benzoic acid 
• 5216-25-1 4-chlorotrichloromethylbenzene 
• 367-11-3 ortho-difluorobenzene 
• 62-53-3 aniline 
• 371-40-4 4-fluoroaniline 
• 85118-04-3 (3,4-difluoro-phenyl)-amide 

Downstream Products

• 1494-94-6 1-(3,4-difluoro-phenyl)-2,5-dimethyl-pyrrole 
• 155857-44-6 (3,4-Difluoro-phenyl)-[4-methoxy-7-(3-methoxy-8-methyl-7,8,9,10-tetrahydro-6H-2-oxa-8-aza-cycloocta[cd]inden-7-yl)-1,1-dioxo-1H-1λ⁶-benzo[b]thiophen-3-yl]-amine 
• 216252-52-7 2-amino-4,5-difluorobenzene-1-sulfonyl chloride 
• 257929-17-2 2-(cyclopent-2-enyl)-4,5-difluoroaniline 
• 850211-99-3 ethyl 1-(3-(5-amino-4-[2-di(ethylsulfanyl)methyl-(2S)-tetrahydro-1H-1-pyrrolylcarbonyl]-2-methoxyphenoxy)propyl)-6,7-difluoro-4-oxo-1,4-dihydro-3-quinolinecarboxylate 
• 850211-97-1 ethyl 1-(3-(4-[2-di(ethylsulfanyl)methyl-(2S)-tetrahydro-1H-1-pyrrolylcarbonyl]-2-methoxy-5-nitrophenoxy)propyl)-6,7-difluoro-4-oxo-1,4-dihydro-3-quinolinecarboxylate 
• 850212-13-4 ethyl 1-(4-(4-[2-di(ethylsulfanyl)methyl-(2S)-tetrahydro-1H-1-pyrrolylcarbonyl]-2-methoxy-5-nitrophenoxy)butyl)-6,7-difluoro-4-oxo-1,4-dihydro-3-quinolinecarboxylate 
• 850212-06-5 ethyl 1-(4-(5-amino-4-[2-di(ethylsulfanyl)methyl-(2S)-tetrahydro-1H-1-pyrrolylcarbonyl]-2-methoxyphenoxy)butyl)-6,7-difluoro-4-oxo-1,4-dihydro-3-quinolinecarboxylate 
• 850212-08-7 ethyl 1-(5-(5-amino-4-[2-di(ethylsulfanyl)methyl-(2S)-tetrahydro-1H-1-pyrrolylcarbonyl]-2-methoxyphenoxy)pentyl)-6,7-difluoro-4-oxo-1,4-dihydro-3-quinolinecarboxylate 
• 850212-04-3 ethyl 1-(5-(4-[2-di(ethylsulfanyl)methyl-(2S)-tetrahydro-1H-1-pyrrolylcarbonyl]-2-methoxy-5-nitrophenoxy)pentyl)-6,7-difluoro-4-oxo-1,4-dihydro-3-quinolinecarboxylate 
• 212519-98-7 2-(3-{3-[(E)-2-(6,7-Difluoro-quinolin-2-yl)-vinyl]-phenyl}-3-oxo-propyl)-benzoic acid methyl ester 
• 573997-37-2 4-Chloro-N-(3,4-difluoro-phenyl)-butyramide 

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