2106-04-9

Basic information

• Product Name: 3-Chloro-2-fluoroaniline
• Synonyms: 3-CHLORO-2-FLUOROANILINE;BUTTPARK 29\01-51;TIMTEC-BB SBB004108;3-Chloro-2-fluoroaniline 97%;3-Chloro-2-fluoroaniline97%;3-chloro-2-fluoro-benzenamin;3-Chloro-2-fluoroaniline,98%;3-Amino-2-fluorochlorobenzene
• CAS NO: 2106-04-9
• Molecular Formula: C₆H₅ClFN
• Molecular Weight: 145.56
• EINECS: 218-283-6
• Product Categories: Anilines, Aromatic Amines and Nitro Compounds;Aniline;Amines;C2 to C6;Nitrogen Compounds
• Mol File: 2106-04-9.mol
• Article Data: 2

Chemical Properties

• Boiling Point: 214 °C(lit.)
• Flash Point: 230 °F
• Appearance: clear light beige liquid
• Density: 1.324 g/mL at 25 °C(lit.)
• Vapor Pressure: 0.125mmHg at 25°C
• Refractive Index: n20/D 1.564(lit.)
• Storage Temp.: Keep in dark place,Inert atmosphere,Room temperature
• PKA: 2.15±0.10(Predicted)
• CAS DataBase Reference: 3-Chloro-2-fluoroaniline(CAS DataBase Reference)
• NIST Chemistry Reference: 3-Chloro-2-fluoroaniline(2106-04-9)
• EPA Substance Registry System: 3-Chloro-2-fluoroaniline(2106-04-9)

Safety Data

• Hazard Codes: Xi,T,Xn
• Statements: 36/37/38-20/21/22-41-37/38-22-23/24/25
• Safety Statements: 26-36-36/37/39-39-45
• WGK Germany: 3
• TSCA: Yes
• HazardClass: 6.1
• Hazardous Substances Data: 2106-04-9(Hazardous Substances Data)

Usage

Chemical Properties

clear light beige liquid

Uses

3-Chloro-2-fluoroaniline may be used in the preparation of 2-chloro-3-fluorobromobenzene and 4-((3-chloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl acetate.

General Description

3-Chloro-2-fluoroaniline is a dihalo-substituted aniline. Its enthalpy of vaporization at boiling point (487.15K) is 42.561kjoule/mol.

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

Synthetic route

1-chloro-2-fluoro-3-nitrobenzene (2106-49-2) → 3-chloro-2-fluoroaniline (2106-04-9)

Conditions	Yield
With iron

1,2-Dichloro-3-nitrobenzene (3209-22-1) → 3-chloro-2-fluoroaniline (2106-04-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: dimethylformamide; potassium fluoride / 150 °C 2: iron View Scheme

4-chloro-7-methoxy-6-{[(2S)-1-tert-butoxycarbonylpyrrolidin-2-yl]methoxy}quinazoline + 3-chloro-2-fluoroaniline (2106-04-9) → 4-(3-chloro-2-fluoroanilino)-7-methoxy-6-{[(2S)-pyrrolidin-2-yl]methoxy}quinazoline hydrochloride

Conditions	Yield
With hydrogenchloride In 1,4-dioxane for 1h; Heating / reflux;	100%

3-chloro-2-fluoroaniline (2106-04-9) + acetic anhydride (108-24-7) → N-(3-chloro-2-fluorophenyl)acetamide (395-36-8)

Conditions	Yield
for 2h; Reflux;	100%
With sodium hydroxide; acetic acid

3-chloro-2-fluoroaniline (2106-04-9) + 6-acetoxy-4-chloro-7-methoxyquinazoline (230955-75-6) → 4-((3-chloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl acetate (740081-22-5)

Conditions	Yield
In acetonitrile at 80℃;	99%
In isopropyl alcohol Heating;	98%
In isopropyl alcohol for 3h; Reflux;	93%

3-chloro-2-fluoroaniline (2106-04-9) + 4-chloro-6-nitro-7-methoxyquinazoline (55496-69-0) → 4-[(3-chloro-2-fluorophenyl)amino]-7-methoxy-6-nitroquinazoline

Conditions	Yield
In acetonitrile at 80℃; for 0.5h;	99%
With acetic acid; triethylamine for 48h;	94%

3-chloro-2-fluoroaniline (2106-04-9) + Ethyl oxalyl chloride (4755-77-5) → ethyl 2-((3-chloro-2-fluorophenyl)amino)-2-oxoacetate

Conditions	Yield
With triethylamine In tetrahydrofuran at 0 - 20℃; for 1h;	98%

4-chloro-7-fluoro-6-nitroquinazoline hydrochloride (1000397-30-7) + 3-chloro-2-fluoroaniline (2106-04-9) → N-(3-chloro-2-fluorophenyl)-7-fluoro-6-nitroquinazolin-4-amine hydrochloride (1000397-23-8)

Conditions	Yield
In isopropyl alcohol at 80℃; for 3h;	97%
In isopropyl alcohol Reflux;

3-chloro-2-fluoroaniline (2106-04-9) + orthoformic acid triethyl ester (122-51-0) → N,N'-bis(3-chloro-2-fluoro-phenyl)formamidine (1252041-51-2)

Conditions	Yield
With acetic acid In cyclohexane at 48℃; for 6h; Inert atmosphere; Industrial scale;	96.2%
With acetic acid In cyclohexane at 48℃; for 12h;	93%

3-chloro-2-fluoroaniline (2106-04-9) + 7-benzyloxy-4-chloro-6-methoxyquinazoline (162364-72-9) → 7-(benzyloxy)-N-(3-chloro-2-fluorophenyl)-6-methoxyquinazolin-4-amine hydrochloride (848415-65-6)

Conditions	Yield
With hydrogenchloride In 1,4-dioxane at 80℃;	96%

3-chloro-2-fluoroaniline (2106-04-9) + 6-bromo-4-chloro-7-fluoropyrido[3,2-d]pyrimidine → 6-bromo-N-(3-chloro-2-fluorophenyl)-7-fluoropyrido[3,2-d]pyrimidin-4-amine

Conditions	Yield
In acetonitrile at 25℃; for 1h;	96%

3-chloro-2-fluoroaniline (2106-04-9) + 6-acetoxy-4-chloro-7-methoxyquinazoline (230955-75-6) → 4-((3-chloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-ol (612501-52-7)

Conditions	Yield
With hydrogenchloride In acetonitrile for 1h; Product distribution / selectivity; Heating / reflux;	95%

4-chloro-6-iodoquinazoline (98556-31-1) + 3-chloro-2-fluoroaniline (2106-04-9) → N-(3-chloro-2-fluorophenyl)-6-iodoquinazolin-4-amine

Conditions	Yield
In isopropyl alcohol at 80℃; for 2h;	95%

3-chloro-2-fluoroaniline (2106-04-9) + N,N-dimethyl-formamide dimethyl acetal (4637-24-5) → N'-(3-chloro-2-fluoro-phenyl)-N,N-dimethyl-formamidine (1252041-52-3)

Conditions	Yield
With acetic acid In 2-methyltetrahydrofuran at 76℃; for 3h;	93%

3-chloro-2-fluoroaniline (2106-04-9) + 6-acetoxy-4-chloro-7-methoxyquinazoline (230955-75-6) → 4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl acetate monohydrochloride (612501-80-1)

Conditions	Yield
In isopropyl alcohol at 80℃; for 3h; Heating / reflux;	92%
In isopropyl alcohol at 80℃; for 3h;	92%
In isopropyl alcohol at 80℃; for 3h; Inert atmosphere;	92%

6-[1-(tert-butoxycarbonyl)piperidin-3-yloxy]-4-chloro-7-methoxyquinazoline (612501-69-6) + 3-chloro-2-fluoroaniline (2106-04-9) → 4-(3-chloro-2-fluoroanilino)-7-methoxy-6-(piperidin-3-yloxy)quinazoline dihydrochloride

Conditions	Yield
With hydrogenchloride In 1,4-dioxane; acetonitrile for 1h; Heating / reflux;	91%

ethyl 4-chloro-6,7-dimethoxycinnoline-3-carboxylatre (1041853-11-5) + 3-chloro-2-fluoroaniline (2106-04-9) → ethyl 4-[(3-chloro-2-fluorophenyl)amino]-6,7-dimethoxycinnoline-3-carboxylate (1041853-33-1)

Conditions	Yield
With acetic acid In ethanol at 75℃;	88%

3-chloro-2-fluoroaniline (2106-04-9) + benzoyl chloride (98-88-4) → N-(3-chloro-2-fluorophenyl)benzamide

Conditions	Yield
With sodium hydroxide In water; toluene at 60℃; for 2h; pH=8;	87%

3-chloro-2-fluoroaniline (2106-04-9) + potassium ethyl xanthogenate (140-89-6) → 2-mercapto-7-chlorobenzothiazole (1849-73-6)

Conditions	Yield
In N,N-dimethyl-formamide at 120 - 130℃; Inert atmosphere;	87%

3-chloro-2-fluoroaniline (2106-04-9) + ethyl 5-chloro-1-(3,5-difluorobenzyl)-4-(2-oxoethyl)-1H-pyrazole-3-carboxylate → ethyl 5-chloro-4-(2-((3-chloro-2-fluorophenyl)amino)ethyl)-1-(3,5-difluorobenzyl)-1H-pyrazole-3-carboxylate

Conditions	Yield
Stage #1: 3-chloro-2-fluoroaniline; ethyl 5-chloro-1-(3,5-difluorobenzyl)-4-(2-oxoethyl)-1H-pyrazole-3-carboxylate With acetic acid In 1,2-dichloro-ethane for 0.166667h; Stage #2: With sodium tris(acetoxy)borohydride In 1,2-dichloro-ethane at 30℃; for 3h;	86%

3-chloro-2-fluoroaniline (2106-04-9) + 4-chloro-7,8-dihydro[1,4]-dioxino[2,3-g]quinazoline (52791-05-6) → N-(3-chloro-2-fluorophenyl)-7,8-dihydro[1,4]dioxino[2,3-g]quinazolin-4-amine

Conditions	Yield
Stage #1: 3-chloro-2-fluoroaniline; 4-chloro-7,8-dihydro[1,4]-dioxino[2,3-g]quinazoline In isopropyl alcohol at 80℃; Microwave irradiation; Stage #2: With sodium hydrogencarbonate In water	85%
In N,N-dimethyl-formamide for 24h; Inert atmosphere; Heating;	82%
In N,N-dimethyl-formamide at 60℃; for 24h;	82%

3-chloro-2-fluoroaniline (2106-04-9) + (3S)-1-(tert-butoxycarbonyl)piperidine-3-carboxylic acid (88495-54-9) → C12H14ClFN2O

Conditions	Yield
Stage #1: 3-chloro-2-fluoroaniline; (3S)-1-(tert-butoxycarbonyl)piperidine-3-carboxylic acid With dmap; dicyclohexyl-carbodiimide In dichloromethane at 0 - 20℃; for 13h; Inert atmosphere; Stage #2: With trifluoroacetic acid In dichloromethane at 0 - 20℃; for 22h; Inert atmosphere;	85%

3-chloro-2-fluoroaniline (2106-04-9) + (1-adamantyl)methyl isocyanate (69887-12-3) → 1-(adamantan-1-ylmethyl)-3-(3-chloro-2-fluorophenyl)urea

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 25℃; for 12h;	85%

3-(4-chloro-3-nitrophenyl)-3-fluoro-2-benzofuran-1(3H)-one + 3-chloro-2-fluoroaniline (2106-04-9) → (3-chloro-2-fluorophenyl)-3-(4-chloro-3-nitrophenyl)-3-hydroxy-2,3-dihydro-1H-isoindol-1-one (870605-90-6)

Conditions	Yield
With N,N-dimethyl-aniline In 1,2-dichloro-ethane at 70℃; for 20h;	84%

3-chloro-2-fluoroaniline (2106-04-9) + (R)-4-chloro-7-methoxyquinazolin-6-yl 2,4-dimethylpiperazine-1-carboxylate → (R)-4-((3-chloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl-2,4-dimethylpiperazinyl-1-carboxylic acid ester

Conditions	Yield
In isopropyl alcohol for 3h; Reflux;	83.1%
In isopropyl alcohol for 3h; Reflux;	83.6%

methyl 8-(1-bromoethyl)-2-morpholino-4-oxo-4H-chromene-6-carboxylate (1296271-41-4) + 3-chloro-2-fluoroaniline (2106-04-9) → methyl 8-(1-(3-chloro-2-fluorophenylamino)ethyl)-2-morpholino-4-oxo-4H-chromene-6-carboxylate (1296271-42-5)

Conditions	Yield
In dichloromethane at 20 - 50℃; for 32h;	82%
In dichloromethane at 20 - 50℃; for 32h;	82%

3-chloro-2-fluoroaniline (2106-04-9) + 4(5)formylimidazole (3034-50-2) → (3-chloro-2-fluoro-phenyl)-(3H-imidazol-4-ylmethyl)-amine (1020818-01-2)

Conditions	Yield
Stage #1: 3-chloro-2-fluoroaniline; 4(5)formylimidazole In methanol at 60℃; Stage #2: With sodium tetrahydroborate In methanol at 20℃; for 4h; Stage #3: With water In methanol	81%

3,4-dihydro-4-oxo-6-(1,4-dioxa-spiro[4,5]decan-8-yl-oxy)-7-methoxy-quinazoline (1046452-66-7) + 3-chloro-2-fluoroaniline (2106-04-9) → 4-[(3-chloro-2-fluoro-phenyl)amino]-6-(4-oxo-cyclohexyloxy)-7-methoxy-quinazoline (1046137-42-1)

Conditions	Yield
Stage #1: 3,4-dihydro-4-oxo-6-(1,4-dioxa-spiro[4,5]decan-8-yl-oxy)-7-methoxy-quinazoline With triethylamine; trichlorophosphate In acetonitrile at 40℃; for 2h; Reflux; Stage #2: 3-chloro-2-fluoroaniline With triethylamine at 20 - 40℃; for 5h; Reflux; Stage #3: With hydrogenchloride; sodium hydroxide In dichloromethane; water; isopropyl alcohol	80%
Stage #1: 3,4-dihydro-4-oxo-6-(1,4-dioxa-spiro[4,5]decan-8-yl-oxy)-7-methoxy-quinazoline With triethylamine; trichlorophosphate In acetonitrile at 40℃; for 2h; Inert atmosphere; Reflux; Stage #2: 3-chloro-2-fluoroaniline With triethylamine In acetonitrile at 20 - 40℃; Inert atmosphere; Stage #3: With hydrogenchloride In water; isopropyl alcohol at 20℃;	73%

(2S,4S)-4-(4-chloro-quinazolin-7-yloxy)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (849345-43-3) + 3-chloro-2-fluoroaniline (2106-04-9) → methyl (4S)-4-({4-[(3-chloro-2-fluorophenyl)amino]quinazolin-7-yl}oxy)-L-prolinate (849345-44-4)

Conditions	Yield
Stage #1: (2S,4S)-4-(4-chloro-quinazolin-7-yloxy)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester; 3-chloro-2-fluoroaniline With hydrogenchloride In 1,4-dioxane; acetonitrile for 2h; Heating / reflux; Stage #2: With ammonia In methanol	79%

3-chloro-2-fluoroaniline (2106-04-9) + potassium thioacyanate (333-20-0) + 3,4,5-Trimethoxybenzoyl chloride (4521-61-3) + 3-chloropentane-2,4-dione (1694-29-7) → 2-(3,4,5-trimethoxybenzoylimino)-3-(3-chloro-2-fluorophenyl)-4-methyl-5-acetyl-1,3-thiazoline

Conditions	Yield
Stage #1: potassium thioacyanate; 3,4,5-Trimethoxybenzoyl chloride In acetonitrile Stage #2: 3-chloro-2-fluoroaniline; 3-chloropentane-2,4-dione With 1-methyl-1H-imidazole In acetonitrile at 70 - 80℃; for 1h;	76%

2-hydroxy-4-(2-methoxyethoxy)benzoic acid (761455-13-4) + 3-chloro-2-fluoroaniline (2106-04-9) + 1,1'-carbonyldiimidazole (530-62-1) → N-(3-chloro-2-fluorobenzyl)-2-hydroxy-4-(2-methoxyethoxy)benzamide

Conditions	Yield
Stage #1: 2-hydroxy-4-(2-methoxyethoxy)benzoic acid; 1,1'-carbonyldiimidazole In tetrahydrofuran at 20℃; for 0.166667h; Inert atmosphere; Stage #2: 3-chloro-2-fluoroaniline In tetrahydrofuran at 80℃; Inert atmosphere;	76%

3-chloro-2-fluoroaniline (2106-04-9) + (E)-N'-(2-cyano-4-nitrophenyl)-N,N'-dimethylformimidamide → N-(2-fluoro-3-chlorophenyl)-6-nitroquinazolin-4-amine (1290545-22-0)

Conditions	Yield
With acetic acid for 1h; Reflux;	75%

Upstream product

• 2106-49-2 1-chloro-2-fluoro-3-nitrobenzene 
• 3209-22-1 1,2-Dichloro-3-nitrobenzene 

Downstream Products

• 2317-75-1 ethyl (3-chloro-2-fluorophenyl)carbamate 
• 2794-55-0 N-<2-Fluor3-chlor-phenyl>-carbamidsaeureisopropylester 
• 833451-52-8 6-chloro-N₄-(3-chloro-2-fluorophenyl)pyrimidine-4,5-diamine 
• 1000397-23-8 N-(3-chloro-2-fluorophenyl)-7-fluoro-6-nitroquinazolin-4-amine hydrochloride 
• 757247-98-6 4-amino-2-chloro-3-fluoro-benzaldehyde 
• 144584-65-6 1-bromo-2-fluoro-3-chlorobenzene 
• 1202228-88-3 C₁₄H₈ClF₂N₃ 
• 1296271-42-5 methyl 8-(1-(3-chloro-2-fluorophenylamino)ethyl)-2-morpholino-4-oxo-4H-chromene-6-carboxylate 
• 1037924-99-4 C₁₆H₁₅ClFNO 
• 1386996-06-0 N-(3-chloro-2-fluorophenyl)-N-methyl-2-phenylbutanamide 
• 1386995-86-3 4-chloro-3-ethyl-1-methyl-3-phenylindolin-2-one 
• 1204573-07-8 3-chloro-2-cyclopropylaminobenzenesulfonamide 
• 351003-48-0 3-chloro-2-fluorobenzene-1-sulfonyl chloride 
• 127142-65-8 1-chloro-2-fluoro-3-isothiocyanatobenzene 

Relevant articles and documents

Method for preparing halogenated aniline from halogenated nitrobenzene through catalytic hydrogenation

The invention discloses a method for preparing halogenated aniline from halogenated nitrobenzene through catalytic hydrogenation. The method comprises the following steps: in a reaction kettle, performing liquid phase catalytic hydrogenation reaction to halogenated nitrobenzene under the action of a sulfur-doped carbon material loaded noble metal catalyst, to obtain halogenated aniline shown in the formula (II), wherein the loading quantity of noble metal in the sulfur-doped carbon material loaded noble metal catalyst is 0.1-5wt%. In the method, the catalyst has good stability, the hydrogenation halogen removal side effect can be effectively inhibited under the condition of having no added halogen removal inhibitor, and the product selectivity is high.