6921-22-8

Basic information

• Product Name: 2,3-Difluoronitrobenzene
• Synonyms: 2,3-DIFLUORONITROBENZENE;1,2-difluoro-3-nitrobenzene;2,3-Difluoro-1-Nitrobenzene;Benzene, 1,2-difluoro-3-nitro- (7CI,8CI,9CI);2,3-Difluoronitrobenzene ,98%;Benzene, 1,2-difluoro-3-nitro-
• CAS NO: 6921-22-8
• Molecular Formula: C₆H₃F₂NO₂
• Molecular Weight: 159.09
• EINECS: 230-035-9
• Product Categories: HALIDE;Miscellaneous
• Mol File: 6921-22-8.mol
• Article Data: 5

Chemical Properties

• Boiling Point: 219 °C at 760 mmHg
• Flash Point: 93.1 °C
• Appearance: /
• Density: 1.45 g/cm³
• Vapor Pressure: 0.18mmHg at 25°C
• Refractive Index: 1.509
• Storage Temp.: Room temperature.
• CAS DataBase Reference: 2,3-Difluoronitrobenzene(CAS DataBase Reference)
• NIST Chemistry Reference: 2,3-Difluoronitrobenzene(6921-22-8)
• EPA Substance Registry System: 2,3-Difluoronitrobenzene(6921-22-8)

Safety Data

• Hazard Codes: Xi
• HazardClass: IRRITANT
• Hazardous Substances Data: 6921-22-8(Hazardous Substances Data)

Usage

Chemical Properties

Light yellow transparent liquid

InChI:InChI=1/C6H3F2NO2/c7-4-2-1-3-5(6(4)8)9(10)11/h1-3H

Synthetic route

2,3-difluoroanilline (4519-40-8) → 1,2-difluoro-3-nitrobenzene (6921-22-8)

Conditions	Yield
With dihydrogen peroxide; trifluoroacetic anhydride In dichloromethane; water at 0 - 20℃;	57%
Stage #1: 2,3-difluoroanilline With tetrafluoroboric acid; sodium nitrite In water at 0℃; for 1.33333h; Stage #2: With copper In water for 1.33333h;	25%

triethylsilane (617-86-7) + 2,3,4-trifluoronitrobenzene (771-69-7) → triethylsilyl fluoride (358-43-0) + 1,2-difluoro-3-nitrobenzene (6921-22-8)

Conditions	Yield
With dmap; (1,3-bis(2,4,6-trimethylphenyl)imidazolin-2-ylidene)AuH In dichloromethane at 40℃; for 12h; Inert atmosphere;	A n/a B 53%

2,3,4-trifluoronitrobenzene (771-69-7) → 1,2-difluoro-3-nitrobenzene (6921-22-8)

Conditions	Yield
With 4,5-bis-(di-tert-butyl-phosphanyl)-9,9-dimethyl-9H-xanthene; [t-BuXantphosAu]+[Cl-Au-Cl]-; diphenylsilane; acetic acid In 1,2-dichloro-ethane at 80℃; for 24h; Inert atmosphere;	12 %Spectr.

2,3,4-trifluoronitrobenzene (771-69-7) → 3,4-difluoronitrobenzene (369-34-6) + 1,2-difluoro-3-nitrobenzene (6921-22-8) + 2,3,4-trifluoroaniline (3862-73-5)

Conditions	Yield
With Dimethylphenylsilane; o-phenylenebis(diphenylphosphine); potassium tert-butylate; copper(l) chloride In tetrahydrofuran for 12h; Inert atmosphere; Reflux; Overall yield = 95 %Spectr.; regioselective reaction;

1,2-difluoro-3-nitrobenzene (6921-22-8) + methylamine (74-89-5) → 2-fluoro-N-methyl-6-nitroaniline (182551-18-4)

Conditions	Yield
With potassium carbonate In 1,4-dioxane; ethanol at 20℃; Inert atmosphere;	100%
With lithium aluminium tetrahydride In methanol; ethanol at 70℃; for 0.75h; Inert atmosphere; Sealed tube; UV-irradiation;	100%
In methanol; ethanol at 70℃; for 0.5h; Microwave heating;

1,2-difluoro-3-nitrobenzene (6921-22-8) + phenylmethanethiol (100-53-8) → 2-(benzylsulfanyl)-1-fluoro-3-nitrobenzene (1242618-47-8)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 2h; regioselective reaction;	99%

tert-butyl N-methyl-N-(piperidin-4-ylmethyl)carbamate (138022-04-5) + 1,2-difluoro-3-nitrobenzene (6921-22-8) → tert-butyl (1-(2-fluoro-6-nitrophenyl)piperidin-4-yl)methyl(methyl)carbamate (1350918-33-0)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetonitrile at 80℃; for 18h;	99%

1,2-difluoro-3-nitrobenzene (6921-22-8) + ethanolamine (141-43-5) → 2-[(2-fluoro-6-nitrophenyl)amino]ethanol (796973-02-9)

Conditions	Yield
In ethanol at 20℃;	97%

isonipecotic acid methyl ester (2971-79-1) + 1,2-difluoro-3-nitrobenzene (6921-22-8) → methyl 1-(2-fluoro-6-nitrophenyl)piperidine-4-carboxylate (1350918-47-6)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetonitrile at 80℃;	97%

1,2-difluoro-3-nitrobenzene (6921-22-8) + diethyl malonate (105-53-3) → diethyl (2-fluoro-6-nitrophenyl)malonate

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 65℃;	90%

1,2-difluoro-3-nitrobenzene (6921-22-8) + methyl 3-aminopropanoate hydrochloride (3196-73-4) → 3-(2-fluoro-6-nitrophenylamino)propionic acid methyl ester (877230-84-7)

Conditions	Yield
With potassium fluoride; 18-crown-6 ether; N-ethyl-N,N-diisopropylamine In acetonitrile for 2h; Heating / reflux;	86%

hexane-EtOAc + tert-Butyl ethyl malonate (32864-38-3) + 1,2-difluoro-3-nitrobenzene (6921-22-8) → 4-[1-[4-[N'-(2-methylphenyl)ureido]-2,3-difluorophenylacetyl](4S)-fluoro-2S)-pyrrolidinyl methoxy]benzoic Acid + ethyl 2,3-difluoro-4-nitrophenylacetic acid

Conditions	Yield
With NaH; ammonium chloride; trifluoroacetic acid In dichloromethane; N,N-dimethyl-formamide	A 85% B n/a

1,2-difluoro-3-nitrobenzene (6921-22-8) + Cyclopropylamine (765-30-0) → N-cyclopropyl-2-fluoro-6-nitroaniline (1338482-91-9)

Conditions	Yield
In ethanol at 20℃; for 16h; Inert atmosphere;	81%

1,2-difluoro-3-nitrobenzene (6921-22-8) + 4-benzyloxyphenylhydrazide (128958-65-6) → 4-benzyloxy-N'-(2-fluoro-6-nitrophenyl)benzhydrazide

Conditions	Yield
In dimethyl sulfoxide at 100℃; for 10h;	81%

1,2-difluoro-3-nitrobenzene (6921-22-8) + glycine ethyl ester hydrochloride (623-33-6) → (2-fluoro-6-nitrophenylamino)acetic acid ethyl ester (877230-81-4)

Conditions	Yield
With potassium fluoride; 18-crown-6 ether; N-ethyl-N,N-diisopropylamine In acetonitrile for 3h; Heating / reflux;	73%

(R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3) + 1,2-difluoro-3-nitrobenzene (6921-22-8) → C16H22FN3O4 (1350917-82-6)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetonitrile at 80℃;	72%

1,2-difluoro-3-nitrobenzene (6921-22-8) + (S)-N-(tert-butoxycarbonyl)serine (3262-72-4) → (S)-2-(tert-butoxycarbonylamino)-3-(2-fluoro-6-nitrophenoxy)propanoic acid

Conditions	Yield
Stage #1: (S)-N-(tert-butoxycarbonyl)serine With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 1.16667h; Stage #2: 1,2-difluoro-3-nitrobenzene In N,N-dimethyl-formamide; mineral oil at 0℃; for 2h;	68%

1,2-difluoro-3-nitrobenzene (6921-22-8) + (S)-2-(cyanomethyl)-4-(2-(((S)-1-methylpyrrolidin-2-yl)methoxy)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepan-4-yl)piperazine-1-carboxylic acid benzyl ester → benzyl (2S)-2-(cyanomethyl)-4-[8-(2-fluoro-6-nitrophenyl)-2-[[(2S)-1-methylpyrrolidin-2-yl]methoxy]-5,6,7,9-tetrahydropyrimido[4,5-c]azepin-4-yl]piperazine-1-carboxylate

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetonitrile at 80℃; for 12h;	59%

1,2-difluoro-3-nitrobenzene (6921-22-8) + ethyl 2-hydroxy-2,2-dimethylethanoate (80-55-7) → ethyl2-(2-fluoro-6-nitrophenoxy)-2-methylpropanoate

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 80℃; for 16h;	56.9%

1,2-difluoro-3-nitrobenzene (6921-22-8) → 5-bromo-1,2-difluoro-3-nitrobenzene

Conditions	Yield
Stage #1: 1,2-difluoro-3-nitrobenzene With sulfuric acid; silver sulfate at 20℃; for 0.0833333h; Stage #2: With bromine at 20℃; for 16h;	55%
With N-Bromosuccinimide; sulfuric acid at 60℃; for 6h;	34.51%

1,2-difluoro-3-nitrobenzene (6921-22-8) + malonic acid dimethyl ester (108-59-8) → 2-(2-fluoro-6-nitrophenyl)malonic acid dimethyl ester (866209-62-3)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 65℃; for 24h;	43%
With potassium carbonate In N,N-dimethyl-formamide at 65℃; for 24h;	43%

1,2-difluoro-3-nitrobenzene (6921-22-8) + aniline (62-53-3) → (2-fluoro-6-nitrophenyl)phenylamine (1033225-32-9)

Conditions	Yield
With caesium carbonate In dimethyl sulfoxide at 20 - 90℃; for 7h;	39%

1,2-difluoro-3-nitrobenzene (6921-22-8) + methyl 5-amino-2-pyridinecarboxylate (67515-76-8) → methyl 5-((2-fluoro-6-nitrophenyl)amino)picolinate

Conditions	Yield
With caesium carbonate In dimethyl sulfoxide at 18 - 25℃; for 5h;	27%

1,2-difluoro-3-nitrobenzene (6921-22-8) + guanidine nitrate (113-00-8) → 5-fluoro-1,2,4-benzotriazine-3-amine 1-oxide (196403-29-9)

Conditions	Yield
With potassium tert-butylate 1.) THF, 60 deg C, 6 h, 2.) THF, 2 h; Yield given. Multistep reaction;

formaldehyd (50-00-0) + Glyoxal (131543-46-9) + 1,2-difluoro-3-nitrobenzene (6921-22-8) + 2-chloro-4,4-difluoro-4,5-dihydrospiro[5H-thieno[2,3-c]pyran-7,4'-piperidine] (1307248-44-7) + 3-methyl-1H-pyrazole-4-carbaldehyde (112758-40-4) → 2-chloro-4,4-difluoro-1'-[[1-(2-fluoro-6-imidazol-1-yl-phenyl)-3-methyl-pyrazol-4-yl]methyl]spiro[5H-thieno[2,3-c]pyran-7,4'-piperidine] (1307313-93-4)

Conditions	Yield
Stage #1: 1,2-difluoro-3-nitrobenzene; 3-methyl-1H-pyrazole-4-carbaldehyde With potassium carbonate In acetonitrile at 20℃; Stage #2: 2-chloro-4,4-difluoro-4,5-dihydrospiro[5H-thieno[2,3-c]pyran-7,4'-piperidine] In dichloromethane at 20℃; for 0.5h; Stage #3: formaldehyd; Glyoxal

1,2-difluoro-3-nitrobenzene (6921-22-8) + 3-methyl-1H-pyrazole-4-carbaldehyde (112758-40-4) + methyl chloroformate (79-22-1) + methyl iodide (74-88-4) → methyl N-[3-fluoro-2-(4-formyl-3-methyl-pyrazol-1-yl)phenyl]-N-methyl-carbamate (1307314-35-7) + C14H14FN3O3

Conditions	Yield
Stage #1: 1,2-difluoro-3-nitrobenzene; 3-methyl-1H-pyrazole-4-carbaldehyde With potassium carbonate In acetonitrile at 20℃; Stage #2: With iron; acetic acid In ethanol; water at 90℃; for 2h; Stage #3: methyl chloroformate; methyl iodide

1,2-difluoro-3-nitrobenzene (6921-22-8) + 2-chloro-4,4-difluoro-4,5-dihydrospiro[5H-thieno[2,3-c]pyran-7,4'-piperidine] (1307248-44-7) + 3-methyl-1H-pyrazole-4-carbaldehyde (112758-40-4) + methyl chloroformate (79-22-1) + methyl iodide (74-88-4) → methyl N-[2-[4-[(2-chloro-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-3-methyl-pyrazol-1-yl]-3-fluoro-phenyl]-N-methyl-carbamate (1307313-54-7)

Conditions	Yield
Stage #1: 1,2-difluoro-3-nitrobenzene; 3-methyl-1H-pyrazole-4-carbaldehyde With potassium carbonate In acetonitrile at 20℃; Stage #2: With iron; acetic acid In ethanol; water at 90℃; for 2h; Stage #3: 2-chloro-4,4-difluoro-4,5-dihydrospiro[5H-thieno[2,3-c]pyran-7,4'-piperidine]; methyl chloroformate; methyl iodide

1,2-difluoro-3-nitrobenzene (6921-22-8) + 3-methyl-1H-pyrazole-4-carbaldehyde (112758-40-4) + methyl chloroformate (79-22-1) → methyl N-[3-fluoro-2-(4-formyl-3-methyl-pyrazol-1-yl)phenyl]carbamate (1307314-33-5)

Conditions	Yield
Stage #1: 1,2-difluoro-3-nitrobenzene; 3-methyl-1H-pyrazole-4-carbaldehyde With potassium carbonate In acetonitrile at 20℃; Stage #2: With iron; acetic acid In ethanol; water at 90℃; for 2h; Stage #3: methyl chloroformate With pyridine In dichloromethane at 0 - 20℃; for 0.5h;

1,2-difluoro-3-nitrobenzene (6921-22-8) + 3-methyl-1H-pyrazole-4-carbaldehyde (112758-40-4) → C11H10FN3O + 1-(2-amino-6-fluoro-phenyl)-3-methyl-1H-pyrazole-4-carbaldehyde (1307314-34-6)

Conditions	Yield
Stage #1: 1,2-difluoro-3-nitrobenzene; 3-methyl-1H-pyrazole-4-carbaldehyde With potassium carbonate In acetonitrile at 20℃; Stage #2: With iron; acetic acid In ethanol; water at 90℃; for 2h;

1,2-difluoro-3-nitrobenzene (6921-22-8) + 3-methyl-1H-pyrazole-4-carbaldehyde (112758-40-4) → C11H8FN3O3 + 1-(2-fluoro-6-nitro-phenyl)-3-methyl-1H-pyrazole-4-carbaldehyde (1307314-08-4)

Conditions	Yield
With potassium carbonate In acetonitrile at 20℃;

1,2-difluoro-3-nitrobenzene (6921-22-8) + 2-chloro-4,4-difluoro-4,5-dihydrospiro[5H-thieno[2,3-c]pyran-7,4'-piperidine] (1307248-44-7) + 3-methyl-1H-pyrazole-4-carbaldehyde (112758-40-4) → 2-chloro-4,4-difluoro-1'-[[1-(2-fluoro-6-nitro-phenyl)-3-methyl-pyrazol-4-yl]methyl]spiro[5H-thieno[2,3-c]pyran-7,4'-piperidine] (1307314-64-2) + C22H20ClF3N4O3S

Conditions	Yield
Stage #1: 1,2-difluoro-3-nitrobenzene; 3-methyl-1H-pyrazole-4-carbaldehyde With potassium carbonate In acetonitrile at 20℃; Stage #2: 2-chloro-4,4-difluoro-4,5-dihydrospiro[5H-thieno[2,3-c]pyran-7,4'-piperidine] In dichloromethane at 20℃; for 0.5h; Stage #3: With sodium tris(acetoxy)borohydride In dichloromethane at 20℃;

1,2-difluoro-3-nitrobenzene (6921-22-8) + 2-chloro-4,4-difluoro-4,5-dihydrospiro[5H-thieno[2,3-c]pyran-7,4'-piperidine] (1307248-44-7) + 3-methyl-1H-pyrazole-4-carbaldehyde (112758-40-4) → C22H22ClF3N4OS + 2-[4-[(2-chloro-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-3-methyl-pyrazol-1-yl]-3-fluoro-aniline (1307314-65-3)

Conditions	Yield
Stage #1: 1,2-difluoro-3-nitrobenzene; 3-methyl-1H-pyrazole-4-carbaldehyde With potassium carbonate In acetonitrile at 20℃; Stage #2: 2-chloro-4,4-difluoro-4,5-dihydrospiro[5H-thieno[2,3-c]pyran-7,4'-piperidine] In dichloromethane at 20℃; for 0.5h;

Upstream product

• 4519-40-8 2,3-difluoroanilline 
• 771-69-7 2,3,4-trifluoronitrobenzene 
• 617-86-7 triethylsilane 

Downstream Products

• 1307313-93-4 2-chloro-4,4-difluoro-1'-[[1-(2-fluoro-6-imidazol-1-yl-phenyl)-3-methyl-pyrazol-4-yl]methyl]spiro[5H-thieno[2,3-c]pyran-7,4'-piperidine] 
• 1307314-35-7 methyl N-[3-fluoro-2-(4-formyl-3-methyl-pyrazol-1-yl)phenyl]-N-methyl-carbamate 
• 1307313-54-7 methyl N-[2-[4-[(2-chloro-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-3-methyl-pyrazol-1-yl]-3-fluoro-phenyl]-N-methyl-carbamate 
• 1307314-33-5 methyl N-[3-fluoro-2-(4-formyl-3-methyl-pyrazol-1-yl)phenyl]carbamate 
• 1307314-34-6 1-(2-amino-6-fluoro-phenyl)-3-methyl-1H-pyrazole-4-carbaldehyde 
• 1307314-08-4 1-(2-fluoro-6-nitro-phenyl)-3-methyl-1H-pyrazole-4-carbaldehyde 
• 1307314-64-2 2-chloro-4,4-difluoro-1'-[[1-(2-fluoro-6-nitro-phenyl)-3-methyl-pyrazol-4-yl]methyl]spiro[5H-thieno[2,3-c]pyran-7,4'-piperidine] 
• 1307314-65-3 2-[4-[(2-chloro-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-3-methyl-pyrazol-1-yl]-3-fluoro-aniline 
• 1357192-60-9 4′-fluoro-5′-[5-methoxy-4-oxo-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-1(4H)-yl]-1'-methylspiro[cyclobutane-1,3'-indol]-2'(1'H)-one 
• 1357192-61-0 methyl 1-(2-fluoro-6-nitrophenyl)cyclobutanecarboxylate 
• 1357192-62-1 methyl (2-fluoro-6-nitrophenyl)acetate 
• 136916-19-3 (2-fluoro-6-nitrophenyl)acetic acid 

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