64182-61-2

Basic information

• Product Name: 2-Chloro-6-fluoronitrobenzene
• Synonyms: 6-chloro-2-fluoro-nitrobenzene;2-CHLORO-6-FLUORONITROBENZENE;1-chloro-3-fluoro-2-nitrobenzene;2-fluoro-6-chloronitrobenzene;1-Fluoro-2-nitro-3-chlorobenzene;2-Chloro-6-fluoronitrobenzene, 97+%;Benzene, 1-chloro-3-fluoro-2-nitro-
• CAS NO: 64182-61-2
• Molecular Formula: C₆H₃ClFNO₂
• Molecular Weight: 175.54
• EINECS: 264-723-5
• Mol File: 64182-61-2.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 245.1 °C at 760 mmHg
• Flash Point: 102 °C
• Appearance: /
• Density: 1.494 g/cm³
• Vapor Pressure: 0.0459mmHg at 25°C
• Refractive Index: 1.554
• Storage Temp.: Sealed in dry,Room Temperature
• CAS DataBase Reference: 2-Chloro-6-fluoronitrobenzene(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Chloro-6-fluoronitrobenzene(64182-61-2)
• EPA Substance Registry System: 2-Chloro-6-fluoronitrobenzene(64182-61-2)

Safety Data

• Hazard Codes: Xi
• Hazardous Substances Data: 64182-61-2(Hazardous Substances Data)

Usage

Chemical Properties

Pale yellow liquid

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

Synthetic route

2-chloro-4-fluoro-3-nitrobenzoic acid → 1-chloro-3-fluoro-2-nitrobenzene (64182-61-2)

Conditions	Yield
With sulfolane; sodium hydrogencarbonate at 195℃; for 2h; Temperature; Reagent/catalyst;	92%

2-chloro-6-fluoroaniline (363-51-9) → 1-chloro-3-fluoro-2-nitrobenzene (64182-61-2)

Conditions	Yield
Stage #1: 2-chloro-6-fluoroaniline With tetrafluoroboric acid; sodium nitrite at 0℃; for 0.5h; Stage #2: With copper; sodium nitrite at 20℃; for 1h; Further stages.;	44%

2-chloro-6-fluoroaniline hydrochloride (59772-34-8) → 1-chloro-3-fluoro-2-nitrobenzene (64182-61-2)

Conditions	Yield
With hydrogenchloride; sodium nitrite In water

1-chloro-3-fluoro-2-nitrobenzene (64182-61-2) + aniline (62-53-3) → (3-chloro-2-nitro-phenyl)-phenyl-amine

Conditions	Yield
Stage #1: aniline With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; for 0.5h; Inert atmosphere; Stage #2: 1-chloro-3-fluoro-2-nitrobenzene In tetrahydrofuran at -78 - 20℃; Stage #3: With ammonium chloride In tetrahydrofuran; water	100%
With potassium tert-butylate In dimethyl sulfoxide at 20℃; for 3h;

1-chloro-3-fluoro-2-nitrobenzene (64182-61-2) + ethylamine (75-04-7) → 3-chloro-N-ethyl-2-nitroaniline

Conditions	Yield
at 40℃; for 16h;	98%

1-chloro-3-fluoro-2-nitrobenzene (64182-61-2) + phenol (108-95-2) → 1-chloro-2-nitro-3-phenoxybenzene (104272-69-7)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 100℃;	98%

1-chloro-3-fluoro-2-nitrobenzene (64182-61-2) → 2-nitro-3-chlorophenol (17802-02-7)

Conditions	Yield
With lithium hydroxide; dihydrogen peroxide In tetrahydrofuran; water at 60℃; for 72h;	97%
Stage #1: 1-chloro-3-fluoro-2-nitrobenzene With lithium hydroxide; water; dihydrogen peroxide In tetrahydrofuran at 60℃; for 72h; Sealed vessel; Stage #2: With hydrogenchloride In tetrahydrofuran; water pH=< 3;	97%
Stage #1: 1-chloro-3-fluoro-2-nitrobenzene With lithium hydroxide; water; dihydrogen peroxide In tetrahydrofuran at 60℃; for 72h; Sealed; Stage #2: With hydrogenchloride In tetrahydrofuran; water pH=< 3;	97%

1-chloro-3-fluoro-2-nitrobenzene (64182-61-2) + 1-(tert-butoxycarbonyl)-4-aminopiperidine (87120-72-7) → tert-butyl 4-((3-chloro-2-nitrophenyl)amino)piperidine-1-carboxylate

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; Inert atmosphere;	93%
With potassium carbonate In dimethyl sulfoxide at 20℃; Inert atmosphere;

2-methyl-1H-indole (95-20-5) + 1-chloro-3-fluoro-2-nitrobenzene (64182-61-2) → 1-(3-chloro-2-nitrophenyl)-2-methyl-1H-indole

Conditions	Yield
With sodium hydroxide In dimethyl sulfoxide at 20℃; for 4h;	90%

1-[trans-4-(methyloxy)-1-methylcyclohexyl]-4-piperidinamine dihydrochloride + 1-chloro-3-fluoro-2-nitrobenzene (64182-61-2) → N-(5-chloro-2-nitrophenyl)-1-[trans-1-methyl-4-(methyloxy)cyclohexyl]-4-piperidinamine (950773-08-7)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20 - 110℃; for 1h; Microwave reactor;	85%

1-chloro-3-fluoro-2-nitrobenzene (64182-61-2) + 1-pentanamine (110-58-7) → 3-chloro-2-nitro-N-pentylaniline

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide at 60℃; for 12h;	83%

di-tert-butyl dicarbonate (24424-99-5) + 1-chloro-3-fluoro-2-nitrobenzene (64182-61-2) → (2-chloro-6-fluoro-phenyl)-carbamic acid tert-butyl ester

Conditions	Yield
With tin; ammonium chloride In methanol at 25℃; for 5h; Sonication;	82%

1-chloro-3-fluoro-2-nitrobenzene (64182-61-2) + chloroformic acid ethyl ester (541-41-3) → (2-chloro-6-fluoro-phenyl)-carbamic acid ethyl ester

Conditions	Yield
With tin; ammonium chloride In methanol at 25℃; for 3.5h; Sonication;	80%

1-chloro-3-fluoro-2-nitrobenzene (64182-61-2) + 4-methoxyphenylacetylen (768-60-5) → 1-chloro-3-[(4-methoxyphenyl)ethynyl]-2-nitrobenzene

Conditions	Yield
With sodium hexamethyldisilazane In tetrahydrofuran at 60℃;	71%

1-chloro-3-fluoro-2-nitrobenzene (64182-61-2) + tri-n-butyl(vinyl)tin (7486-35-3) → 1-fluoro-2-nitro-3-vinylbenzene (1112241-39-0)

Conditions	Yield
With bis(tri-t-butylphosphine)palladium(0); cesium fluoride In 1,4-dioxane at 100℃; for 26h;	70.6%

1-chloro-3-fluoro-2-nitrobenzene (64182-61-2) + (S)-3-amino-2-tert-butoxycarbonylaminopropionic acid (76387-70-7) → (S)-2-((tert-butoxycarbonyl)amino)-3-((3-chloro-2-nitrophenyl)amino)propanoic acid (1584150-11-7)

Conditions	Yield
With potassium carbonate In ethanol at 80℃; for 9h; Inert atmosphere;	62%

aminomethylphosphonic acid diethyl ester (50917-72-1) + 1-chloro-3-fluoro-2-nitrobenzene (64182-61-2) → [(3-chloro-2-nitro-phenylamino)-methyl]-phosphonic acid diethyl ester (345203-15-8)

Conditions	Yield
In toluene for 8h; Heating;	45%

4-(1,3,4-oxadiazol-2-yl)-phenol (5378-27-8) + 1-chloro-3-fluoro-2-nitrobenzene (64182-61-2) → 2-(4-(3-chloro-2-nitrophenoxy)phenyl)-1,3,4-oxadiazole

Conditions	Yield
Stage #1: 4-(1,3,4-oxadiazol-2-yl)-phenol With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 0.5h; Inert atmosphere; Stage #2: 1-chloro-3-fluoro-2-nitrobenzene In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; Inert atmosphere;	28%

1-chloro-3-fluoro-2-nitrobenzene (64182-61-2) → [(3-chloro-2-amino-phenylamino)-methyl]-phosphonic acid diethyl ester (345203-17-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 45 percent / toluene / 8 h / Heating 2: 89 percent / H2 / Rh/C / ethanol / 24 h / 760.05 Torr View Scheme

1-chloro-3-fluoro-2-nitrobenzene (64182-61-2) → [R(-)]-2-amino-3-[4-chloro-1-(diethoxy-phosphorylmethyl)-1H-benzoimidazol-2-yl]-propionic acid (345203-21-6)

Conditions	Yield
Multi-step reaction with 5 steps 1: 45 percent / toluene / 8 h / Heating 2: 89 percent / H2 / Rh/C / ethanol / 24 h / 760.05 Torr 3: 61 percent / diisopropylethylamine; bis(2-oxo-3-oxazolidinyl)phosphinic chloride / CH2Cl2 / 0 °C 4: 51 percent / p-toluenesulfonic acid monohydrate / toluene / 2 h / Heating 5: 94 percent / acetic acid; H2 / Pd/C / 4 h View Scheme

1-chloro-3-fluoro-2-nitrobenzene (64182-61-2) → [R(-)]-2-amino-3-(4-chloro-1-phosphonomethyl-1H-benzoimidazol-2-yl)-propionic acid hydrochloride

Conditions

Yield

Multi-step reaction with 6 steps 1: 45 percent / toluene / 8 h / Heating 2: 89 percent / H2 / Rh/C / ethanol / 24 h / 760.05 Torr 3: 61 percent / diisopropylethylamine; bis(2-oxo-3-oxazolidinyl)phosphinic chloride / CH2Cl2 / 0 °C 4: 51 percent / p-toluenesulfonic acid monohydrate / toluene / 2 h / Heating 5: 94 percent / acetic acid; H2 / Pd/C / 4 h 6: 39 percent / aq. HCl / 0.75 h / Heating View Scheme

1-chloro-3-fluoro-2-nitrobenzene (64182-61-2) → [R(-)]-2-(benzyloxycarbonylamino)-3-[1-(4-chloro-1-diethoxy-phosphorylmethyl)-1H-benzoimidazol-2-yl]-propionic acid benzyl ester (345203-19-2)

Conditions	Yield
Multi-step reaction with 4 steps 1: 45 percent / toluene / 8 h / Heating 2: 89 percent / H2 / Rh/C / ethanol / 24 h / 760.05 Torr 3: 61 percent / diisopropylethylamine; bis(2-oxo-3-oxazolidinyl)phosphinic chloride / CH2Cl2 / 0 °C 4: 51 percent / p-toluenesulfonic acid monohydrate / toluene / 2 h / Heating View Scheme

1-chloro-3-fluoro-2-nitrobenzene (64182-61-2) → [R(-)]-2-benzyloxycarbonylamino-N-{2-chloro-6-[(diethoxy-phosphorylmethyl)-amino]-phenyl}-succinamic acid benzyl ester (345203-18-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: 45 percent / toluene / 8 h / Heating 2: 89 percent / H2 / Rh/C / ethanol / 24 h / 760.05 Torr 3: 61 percent / diisopropylethylamine; bis(2-oxo-3-oxazolidinyl)phosphinic chloride / CH2Cl2 / 0 °C View Scheme

4-carbobenzoxypiperazine-2-carboxylic acid hydrochloride + 1-chloro-3-fluoro-2-nitrobenzene (64182-61-2) → 4-Carbobenzoxy-1-(3-Chloro-2-Nitrophenyl)Piperazine-2-Carboxylic Acid (64182-62-3)

methyl 5-aminothiophene-2-carboxylate (14597-58-1) + 1-chloro-3-fluoro-2-nitrobenzene (64182-61-2) → C12H9ClN2O4S (1314092-10-8)

Conditions	Yield
With triethylbutylammonium chloride; potassium hydroxide In N,N-dimethyl-formamide at 0 - 20℃;

1-chloro-3-fluoro-2-nitrobenzene (64182-61-2) → (S)-1-(4-chloro-1-phenyl-1H-benzoimidazol-2-yl)ethylamine (1393176-11-8)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: lithium hexamethyldisilazane / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 1.2: -78 - 20 °C 2.1: ammonium chloride; iron / water; methanol / 3 h / Reflux 3.1: 1-hydroxy-7-aza-benzotriazole; triethylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 0 - 20 °C / Inert atmosphere 4.1: acetic acid / 18 h / 65 °C 5.1: trifluoroacetic acid / dichloromethane / 0.33 h / 20 °C View Scheme

1-chloro-3-fluoro-2-nitrobenzene (64182-61-2) → 3-chloro-N1-phenyl-o-phenylenediamine (109174-62-1)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: lithium hexamethyldisilazane / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 1.2: -78 - 20 °C 2.1: ammonium chloride; iron / water; methanol / 3 h / Reflux View Scheme

1-chloro-3-fluoro-2-nitrobenzene (64182-61-2) → [(S)-1-(2-chloro-6-phenylaminophenylcarbamoyl)ethyl]carbamic acid tert-butyl ester (1393176-12-9)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: lithium hexamethyldisilazane / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 1.2: -78 - 20 °C 2.1: ammonium chloride; iron / water; methanol / 3 h / Reflux 3.1: 1-hydroxy-7-aza-benzotriazole; triethylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 0 - 20 °C / Inert atmosphere View Scheme

1-chloro-3-fluoro-2-nitrobenzene (64182-61-2) → [(S)-1-(4-chloro-1-phenyl-1H-benzoimidazol-2-yl)ethyl]carbamic acid tert-butyl ester (1393176-13-0)

Conditions

Yield

Multi-step reaction with 4 steps 1.1: lithium hexamethyldisilazane / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 1.2: -78 - 20 °C 2.1: ammonium chloride; iron / water; methanol / 3 h / Reflux 3.1: 1-hydroxy-7-aza-benzotriazole; triethylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 0 - 20 °C / Inert atmosphere 4.1: acetic acid / 18 h / 65 °C View Scheme

Upstream product

• 59772-34-8 2-chloro-6-fluoroaniline hydrochloride 
• 363-51-9 2-chloro-6-fluoroaniline 

Downstream Products

• 345203-17-0 [(3-chloro-2-amino-phenylamino)-methyl]-phosphonic acid diethyl ester 
• 345203-19-2 [R(-)]-2-(benzyloxycarbonylamino)-3-[1-(4-chloro-1-diethoxy-phosphorylmethyl)-1H-benzoimidazol-2-yl]-propionic acid benzyl ester 
• 345203-18-1 [R(-)]-2-benzyloxycarbonylamino-N-{2-chloro-6-[(diethoxy-phosphorylmethyl)-amino]-phenyl}-succinamic acid benzyl ester 
• 64182-62-3 4-Carbobenzoxy-1-(3-Chloro-2-Nitrophenyl)Piperazine-2-Carboxylic Acid 
• 1112241-39-0 1-fluoro-2-nitro-3-vinylbenzene 
• 1464832-61-8 2-((1S)-1-(5-chloro-3-(2-(methylthio)phenyl)quinoxalin-2-yl)ethyl)isoindoline-1,3-dione 
• 1464832-62-9 2-((1S)-1-(5-chloro-3-(2-(methylsulfonyl)phenyl)quinoxalin-2-yl)ethyl)-isoindoline-1,3-dione 
• 1464832-63-0 (S)-1-(5-chloro-3-(2-(methylsulfonyl)phenyl)quinoxalin-2-yl)ethanamine 
• 1464832-51-6 (S)-4-amino-6-((1-(5-chloro-3-(2-(methylsulfonyl)-phenyl)quinoxalin-2-yl)ethyl)amino)pyrimidine-5-carbonitrile 
• 1464832-65-2 2-((S)-1-(1,3-dioxoisoindolin-2-yl)ethyl)-3-(2-(methylsulfonyl)phenyl)-quinoxaline-5-carbonitrile 
• 1464832-66-3 2-((S)-1-aminoethyl)-3-(2-(methylsulfonyl)phenyl)quinoxaline-5-carbonitrile 
• 1464832-64-1 2-((S)-1-(6-amino-5-cyanopyrimidin-4-ylamino)-ethyl)-3-(2-(methylsulfonyl)phenyl)quinoxaline-5-carbonitrile 
• 1464832-52-7 2-((3-chloro-2-nitrophenyl)amino)butanoic acid 
• 17802-02-7 2-nitro-3-chlorophenol 

Relevant articles and documents

Preparation method of substituted nitrobenzene compound

The invention discloses a preparation method of a substituted nitrobenzene compound. The method comprises the following steps: carrying out a decarboxylation reaction as shown below on a compound II under the action of alkali in a solvent at the temperature of 150 to 250 DEG C to obtain a compound I; the alkali is one or more of carbonates and bicarbonates of alkali metals. Compared with some metal-catalyzed decarboxylation methods, the preparation method of the substituted nitrobenzene compound has the advantages of simple operation, low production cost, convenient post-treatment and high yield, and more application values in industrial production.

2,3,4,4A-Tetrahydro-1H-pyrazino[1,2-a,]quinoxalin-5(6H)-ones and derivatives thereof for relieving hypertension

Compounds of the formula STR1 wherein R is hydrogen (lower)alkyl, phen(lower)alkyl, benzoyl(lower)alkyl, or p-halobenzoyl(lower)alkyl; R1 is hydrogen or (lower)alkyl; R2 is hydrogen, (lower)alkyl, (lower)alkoxy, chlorine, fluorine, trifluoromethyl, or amino in the 7-, 8-, or 9-position; R3 is hydrogen, or (lower)alkyl; and R4 is hydrogen, (lower)alkyl, (lower)alkoxy, chlorine, fluorine, or trifluoromethyl in the 7-, 8-, or 9-position; or the non-toxic acid addition salts thereof; exert a hypotensive effect in hypertensive animals.