28166-06-5

Basic information

• Product Name: 4-FLUORO-3-NITROPHENYL AZIDE
• Synonyms: FNPA;4-AZIDO-1-FLUORO-2-NITROBENZENE;4-FLUORO-3-NITROPHENYL AZIDE;1-azido-4-fluoro-3-nitro-benzen;1-azido-4-fluoro-3-nitrobenzene;4-FLUORO-3-NITROPHENYL AZIDE FOR PHOTOAF FINITY LABELLING;4-Fluoro-3-nitrophenylazide97%;3-Nitro-4-fluorophenylazide
• CAS NO: 28166-06-5
• Molecular Formula: C₆H₃FN₄O₂
• Molecular Weight: 182.11
• EINECS: 248-878-6
• Product Categories: photoazide
• Mol File: 28166-06-5.mol
• Article Data: 5

Chemical Properties

• Melting Point: 54-56
• Flash Point: 113 °C
• Appearance: /
• Storage Temp.: 2-8°C
• CAS DataBase Reference: 4-FLUORO-3-NITROPHENYL AZIDE(CAS DataBase Reference)
• NIST Chemistry Reference: 4-FLUORO-3-NITROPHENYL AZIDE(28166-06-5)
• EPA Substance Registry System: 4-FLUORO-3-NITROPHENYL AZIDE(28166-06-5)

Safety Data

• Hazard Codes: Xi,T,F
• Statements: 5-11-23/24/25
• Safety Statements: 36/37/39-45
• RIDADR: 1325
• RTECS: CY6620000
• HazardClass: 4.1
• PackingGroup: III
• Hazardous Substances Data: 28166-06-5(Hazardous Substances Data)

Usage

Purification Methods

Dissolve the azide in Et2O, dry it over MgSO4, filter, evaporate and recrystallise the residue from pet ether (b 20-40o) to give orange needles. Store it in a stoppered container at ~0o. The NMR has  7.75 (m 1H) and 7.35 (m 2H) in CDCl3. [Hagedorn et al. J Org Chem 43 2070 1978.]

InChI:InChI=1/C6H4FN4O2/c7-5-2-1-4(9-10-8)3-6(5)11(12)13/h1-3,8H/q+1

Synthetic route

4-Fluoro-3-nitroaniline (364-76-1) → 4-fluoro-3-nitrophenylazide (28166-06-5)

Conditions	Yield
Stage #1: 4-Fluoro-3-nitroaniline With hydrogenchloride; sodium nitrite In water at 70℃; Stage #2: With sodium azide In water at 70℃;	98%
With sodium azide; tert.-butylnitrite In tert-butyl alcohol at 20℃; for 1h;	92%
Stage #1: 4-Fluoro-3-nitroaniline With hydrogenchloride; sodium nitrite In water at 0℃; for 0.25h; Stage #2: With sodium azide In water at 20℃; for 0.5h;	75%
Stage #1: 4-Fluoro-3-nitroaniline With hydrogenchloride; sodium nitrite In water at 5℃; for 0.5h; Cooling with ice; Stage #2: With sodium azide In water at 0℃;	73%
(i) aq. H2SO4, NaNO2, (ii) aq. NaN3; Multistep reaction;

sodium azide + 4-Fluoro-3-nitroaniline (364-76-1) → 4-fluoro-3-nitrophenylazide (28166-06-5)

Conditions	Yield
Stage #1: 4-Fluoro-3-nitroaniline With hydrogenchloride; sodium nitrite In water at 0℃; for 0.166667h; Stage #2: sodium azide In water at 0℃; for 4.25h;

4-fluoro-3-nitrophenylazide (28166-06-5) + (1R,2R,3S,4R,5S)-4-(2-chloro-6-(prop-2-ynylamino)-9H-purin-9-yl)bicyclo[3.1.0]hexane-2,3-diol (1309943-98-3) → (1R,2R,3S,4R,5S)-4-(2-chloro-6-((1-(4-fluoro-3-nitrophenyl)-1H-1,2,3-triazol-4-yl)methylamino)-9H-purin-9-yl)bicyclo[3.1.0]hexane-2,3-diol (1309943-99-4)

Conditions	Yield
With copper(II) sulfate; sodium L-ascorbate; tris[(1-benzyl-1H-1,2,3-triazol-4yl)methyl]amine In water; tert-butyl alcohol at 20℃;	96%
With sodium ascorbate; copper(II) sulfate; tris[(1-benzyl-1H-1,2,3-triazol-4yl)methyl]amine In dichloromethane; water; tert-butyl alcohol at 20℃; Inert atmosphere;	96%

4-fluoro-3-nitrophenylazide (28166-06-5) + (1S,2R,3S,4R,5S)-4-[2-chloro-6-(3-(nona-1,8-diynyl)phenylmethylamino)-9H-purin-9-yl]-2,3-dihydroxybicyclo[3.1.0]hexane-1-carboxylic acid N-methylamide (1309943-74-5) → (1S,2R,3S,4R,5S)-4-[2-chloro-6-(3-(7-(1-(4-fluoro-3-nitrophenyl)-1H-1,2,3-triazol-4-yl)hept-1-ynyl)benzylamino)-9H-purin-9-yl]-2,3-dihydroxybicyclo[3.1.0]hexane-1-carboxylic acid N-methylamide (1309943-77-8)

Conditions	Yield
With sodium ascorbate; copper(II) sulfate; tris[(1-benzyl-1H-1,2,3-triazol-4yl)methyl]amine In dichloromethane; water; tert-butyl alcohol at 20℃; Inert atmosphere;	96%

thiobenzoic acid (98-91-9) + 4-fluoro-3-nitrophenylazide (28166-06-5) → N-(4-fluoro-3-nitrophenyl)-benzylamide (228425-41-0)

Conditions	Yield
With 2,6-dimethylpyridine In methanol at 25℃; for 15h;	95%

4-fluoro-3-nitrophenylazide (28166-06-5) + (1R,2R,3S,4R,5S)-4-(2-chloro-6-(3-(octa-1,7-diynyl)benzylamino)-9H-purin-9-yl)bicyclo[3.1.0]hexane-2,3-diol (1309943-87-0) → (1R,2R,3S,4R,5S)-4-(2-chloro-6-(3-(6-(1-(4-fluoro-3-nitrophenyl)-1H-1,2,3-triazol-4-yl)hex-1-ynyl)benzylamino)-9H-purin-9-yl)bicyclo[3.1.0]hexane-2,3-diol (1309943-90-5)

Conditions	Yield
With sodium ascorbate; copper(II) sulfate; tris[(1-benzyl-1H-1,2,3-triazol-4yl)methyl]amine In dichloromethane; water; tert-butyl alcohol at 20℃; Inert atmosphere;	95%

4-fluoro-3-nitrophenylazide (28166-06-5) + thioacetic acid (507-09-5) → N-(4-fluoro-3-nitrophenyl)acetamide (351-32-6)

Conditions	Yield
With 2,6-dimethylpyridine In methanol at 25℃; for 15h;	94%

4-fluoro-3-nitrophenylazide (28166-06-5) + (1'S,2'R,3'S,4'R,5'S)-4'-[6-(3-chlorobenzylamino)-2-(1,7-octadiynyl)-9H-purin-9-yl]-2',3'-dihydroxybicyclo[3.1.0]hexane-1'-carboxylic acid N-methylamide (1213770-15-0) → MRS5223 (1217299-58-5)

Conditions	Yield
With copper(II) sulphate hydrate; sodium L-ascorbate In tetrahydrofuran; water at 20℃; regioselective reaction;	94%
With copper(ll) sulfate pentahydrate; sodium L-ascorbate In tetrahydrofuran; water at 20℃;	94%

4-fluoro-3-nitrophenylazide (28166-06-5) + (1S,2R,3S,4R,5S)-4-[2-chloro-6-(3-(octa-1,7-diynyl)phenylmethylamino)-9H-purin-9-yl]-2,3-dihydroxybicyclo[3.1.0]hexane-1-carboxylic acid N-methylamide (1309944-05-5) → (1S,2R,3S,4R,5S)-4-[2-chloro-6-(3-(6-(1-(4-fluoro-3-nitrophenyl)-1H-1,2,3-triazol-4-yl)hex-1-ynyl)benzylamino)-9H-purin-9-yl]-2,3-dihydroxybicyclo[3.1.0]hexane-1-carboxylic acid N-methylamide (1309943-76-7)

Conditions	Yield
With sodium ascorbate; copper(II) sulfate; tris[(1-benzyl-1H-1,2,3-triazol-4yl)methyl]amine In dichloromethane; water; tert-butyl alcohol at 20℃; Inert atmosphere;	94%

4-fluoro-3-nitrophenylazide (28166-06-5) + (1S,2R,3S,4R,5S)-4-(2-chloro-6-(prop-2-ynylamino)-9H-purin-9-yl)-2,3-dihydroxy-N-methylbicyclo[3.1.0]hexane-1-carboxamide (1309943-94-9) → (1S,2R,3S,4R,5S)-4-(2-chloro-6-((1-(4-fluoro-3-nitrophenyl)-1H-1,2,3-triazol-4-yl)methylamino)-9H-purin-9-yl)-2,3-dihydroxy-N-methylbicyclo[3.1.0]hexane-1-carboxamide (1309943-95-0)

Conditions	Yield
With copper(II) sulfate; sodium L-ascorbate; tris[(1-benzyl-1H-1,2,3-triazol-4yl)methyl]amine In water; tert-butyl alcohol at 20℃;	92%
With sodium ascorbate; copper(II) sulfate; tris[(1-benzyl-1H-1,2,3-triazol-4yl)methyl]amine In dichloromethane; water; tert-butyl alcohol at 20℃; Inert atmosphere;	92%

4-fluoro-3-nitrophenylazide (28166-06-5) + 17α-aminomethyl-3,3-(dimethoxy)-5α-androstan-17β-ol (300350-92-9) → 17α-[(N-4-azido-2-nitrophenyl)aminomethyl]-3,3-dimethoxy-5α-androstan-17β-ol (300351-06-8)

Conditions	Yield
With triethylamine In tetrahydrofuran; diethyl ether; ethanol	91%

4-fluoro-3-nitrophenylazide (28166-06-5) + (1R,2R,3S,4R,5S)-4-(2-chloro-6-(3-(hepta-1,6-diynyl)benzylamino)-9H-purin-9-yl)bicyclo[3.1.0]hexane-2,3-diol (1309943-86-9) → (1R,2R,3S,4R,5S)-4-(2-chloro-6-(3-(5-(1-(4-fluoro-3-nitrophenyl)-1H-1,2,3-triazol-4-yl)pent-1-ynyl)benzylamino)-9H-purin-9-yl)bicyclo[3.1.0]hexane-2,3-diol (1309943-89-2)

Conditions	Yield
With copper(II) sulfate; sodium L-ascorbate; tris[(1-benzyl-1H-1,2,3-triazol-4yl)methyl]amine In dichloromethane; water; tert-butyl alcohol at 20℃;	91%
With sodium ascorbate; copper(II) sulfate; tris[(1-benzyl-1H-1,2,3-triazol-4yl)methyl]amine In dichloromethane; water; tert-butyl alcohol at 20℃; Inert atmosphere;	91%

4-fluoro-3-nitrophenylazide (28166-06-5) + (1R,2R,3S,4R,5S)-4-(2-chloro-6-(3-(nona-1,8-diynyl)benzylamino)-9H-purin-9-yl)bicyclo[3.1.0]hexane-2,3-diol (1309943-88-1) → (1R,2R,3S,4R,5S)-4-(2-chloro-6-(3-(7-(1-(4-fluoro-3-nitrophenyl)-1H-1,2,3-triazol-4-yl)hept-1-ynyl)benzylamino)-9H-purin-9-yl)bicyclo[3.1.0]hexane-2,3-diol (1309943-91-6)

Conditions	Yield
With sodium ascorbate; copper(II) sulfate; tris[(1-benzyl-1H-1,2,3-triazol-4yl)methyl]amine In dichloromethane; water; tert-butyl alcohol at 20℃; Inert atmosphere;	91%

4-fluoro-3-nitrophenylazide (28166-06-5) + (1S,2R,3S,4R,5S)-4-[2-chloro-6-(3-(hepta-1,6-diynyl)phenylmethylamino)-9H-purin-9-yl]-2,3-dihydroxybicyclo[3.1.0]hexane-1-carboxylic acid N-methylamide (1309944-03-3) → (1S,2R,3S,4R,5S)-4-[2-chloro-6-(3-(5-(1-(4-fluoro-3-nitrophenyl)-1H-1,2,3-triazol-4-yl)pent-1-ynyl)benzylamino)-9H-purin-9-yl]-2,3-dihydroxybicyclo[3.1.0]hexane-1-carboxylic acid N-methylamide (1309943-75-6)

Conditions	Yield
With copper(II) sulfate; sodium L-ascorbate; tris[(1-benzyl-1H-1,2,3-triazol-4yl)methyl]amine In dichloromethane; water; tert-butyl alcohol at 20℃;	90%
With sodium ascorbate; copper(II) sulfate; tris[(1-benzyl-1H-1,2,3-triazol-4yl)methyl]amine In dichloromethane; water; tert-butyl alcohol at 20℃; Inert atmosphere;	90%

4-fluoro-3-nitrophenylazide (28166-06-5) + ethylenediamine (107-15-3) → 4-(2-aminoethyl)amino-3-nitro-phenylazide (napa) (64309-07-5)

Conditions	Yield
In dichloromethane for 24h; Ambient temperature;	89%
In dichloromethane for 0.5h; Ambient temperature; in the dark;	70%

4-fluoro-3-nitrophenylazide (28166-06-5) + (1'S,2'R,3'S,4'R,5'S)-4'-[6-(3-chlorobenzylamino)-2-(1,6-heptadiynyl)-9H-purin-9-yl]-2',3'-dihydroxybicyclo[3.1.0]hexane-1'-carboxylic acid N-methylamide (1217299-55-2) → (1S,2R,3S,4R,5S)-4-(6-(3-chlorobenzylamino)-2-(5-(1-(4-fluoro-3-nitrophenyl)-1H-1,2,3-triazol-4-yl)pent-1-ynyl)-9H-purin-9-yl)-2,3-dihydroxybicyclo[3.1.0]hexane-1-carboxylic acid N-methylamide (1217299-57-4)

Conditions	Yield
With copper(II) sulphate hydrate; sodium L-ascorbate In tetrahydrofuran; water at 20℃; regioselective reaction;	89%

4-fluoro-3-nitrophenylazide (28166-06-5) + C16H14O7 (1285718-33-3) → C22H17FN4O9 (1285718-37-7)

Conditions	Yield
With copper(ll) sulfate pentahydrate; sodium L-ascorbate In dichloromethane; water at 20℃;	87%

4-fluoro-3-nitrophenylazide (28166-06-5) + 6-methyl-2-oxo-1-(prop-2-yn-1-yl)-4-(trifluoromethyl)-1,2-dihydropyridine-3-carbonitrile (1582270-75-4) → 1-((1-(4-fluoro-3-nitrophenyl)-1H-1,2,3-triazol-4-yl)methyl)-6-methyl-2-oxo-4-(trifluoromethyl)-1,2-dihydropyridine-3-carbonitrile (1582270-94-7)

Conditions	Yield
Stage #1: 6-methyl-2-oxo-1-(prop-2-yn-1-yl)-4-(trifluoromethyl)-1,2-dihydropyridine-3-carbonitrile With copper(l) iodide In tetrahydrofuran at 20℃; for 0.5h; Stage #2: 4-fluoro-3-nitrophenylazide In tetrahydrofuran for 12h;	86%

4-fluoro-3-nitrophenylazide (28166-06-5) + 6-phenyl-2-(prop-2-yn-1-yloxy)-4-(trifluoromethyl)nicotinonitrile (1336913-39-3) → 2-((1-(4-fluoro-3-nitrophenyl)-1H-1,2,3-triazol-4-yl)methoxy)-6-phenyl-4-(trifluoromethyl)nicotinonitrile (1582270-81-2)

Conditions	Yield
Stage #1: 6-phenyl-2-(prop-2-yn-1-yloxy)-4-(trifluoromethyl)nicotinonitrile With copper(l) iodide In tetrahydrofuran at 20℃; for 0.5h; Stage #2: 4-fluoro-3-nitrophenylazide In tetrahydrofuran for 12h;	85%

4-fluoro-3-nitrophenylazide (28166-06-5) + ethyl 2-(prop-2-ynyloxy)-2-(trifluoromethyl)-2H-chromene-3-carboxylate (1591994-08-9) → ethyl 2-((1-(4-fluoro-3-nitrophenyl)-1H-1,2,3-triazole-4-yl)methoxy)-2-(trifluoromethyl)-2H-chromene-3-carboxylate (1591994-28-3)

Conditions	Yield
Stage #1: ethyl 2-(prop-2-ynyloxy)-2-(trifluoromethyl)-2H-chromene-3-carboxylate With copper(l) iodide In tetrahydrofuran at 20℃; for 0.5h; Inert atmosphere; Stage #2: 4-fluoro-3-nitrophenylazide In tetrahydrofuran at 20℃;	82%

4-fluoro-3-nitrophenylazide (28166-06-5) + 12-Aminododecanoic acid (693-57-2) → C18H27N5O4 (58775-40-9)

Conditions	Yield
In methanol; N,N-dimethyl-formamide at 80℃;	80%

1,6-Hexanediamine (124-09-4) + 4-fluoro-3-nitrophenylazide (28166-06-5) → N'-(4-azido-2-nitrophenyl)hexane-1,6-diamine (64309-09-7)

Conditions	Yield
In methanol at 20℃; for 12h; Inert atmosphere;	80%

Geraniol (106-24-1) + 4-fluoro-3-nitrophenylazide (28166-06-5) → p-azido-o-nitrophenyl geranyl ether (106929-46-8)

Conditions	Yield
With potassium tert-butylate In tetrahydrofuran for 14h; Ambient temperature;	76%

4-fluoro-3-nitrophenylazide (28166-06-5) + diethylamine (109-89-7) → 4-(N,N-diethylamino)-3-nitrophenylazide

Conditions	Yield
In acetonitrile at 40℃; for 3h;	67%

4-fluoro-3-nitrophenylazide (28166-06-5) + (8R,9S,13S,14S,16S)-16-(4-Amino-but-2-ynyl)-3-(tert-butyl-dimethyl-silanyloxy)-13-methyl-6,7,8,9,11,12,13,14,15,16-decahydro-cyclopenta[a]phenanthren-17-one (234765-89-0) → 16α-(4-(4-azido-2-nitrophenylamino)-2-butynyl)estra-1,3,5(10)-triene-3,17β-diol

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide for 44h; Ambient temperature;	59.9%

4-fluoro-3-nitrophenylazide (28166-06-5) + histamine dichloride (56-92-8) + water ethanol (180330-54-5) + sodium carbonate (497-19-8) → 4(5)-[2-(4-azido-2-nitroanilino)ethyl]imidazole hydrochloride (79412-26-3)

Conditions	Yield
With hydrogenchloride	58%

6-amino-1-hexanol (4048-33-3) + 4-fluoro-3-nitrophenylazide (28166-06-5) → 6-(4-Azido-2-nitro-phenylamino)-hexan-1-ol

Conditions	Yield
With triethylamine In 1,4-dioxane at 20℃; for 2h;	55%
In 1,4-dioxane
Stage #1: 6-amino-1-hexanol; 4-fluoro-3-nitrophenylazide In 1,4-dioxane at 20℃; for 0.333333h; Stage #2: With triethylamine In 1,4-dioxane at 20 - 55℃; for 16h;	16 g

4-pyrrol-1-yl-butylamine (98492-69-4) + 4-fluoro-3-nitrophenylazide (28166-06-5) → C14H20N6O2

Conditions	Yield
In tetrahydrofuran for 0.5h;	54%

4-fluoro-3-nitrophenylazide (28166-06-5) + 3,3-(dimethoxy)-17α-aminopropyl-17β-hydroxy-5α-androstan-3-one (300350-96-3) → 17α-[(N-4-azido-2-nitrophenyl)aminopropyl]-3,3-dimethoxy-5α-androstan-17β-ol (300351-12-6)

Conditions	Yield
With triethylamine In tetrahydrofuran; diethyl ether; ethanol	47%

4-fluoro-3-nitrophenylazide (28166-06-5) + N-(2-aminoethyl)-N'-cyano-N''-<3-<3-(1-piperidinylmethyl)phenoxy>propyl>guanidine (140872-99-7) → C25H32N10O3 (140873-16-1)

Conditions	Yield
With sodium carbonate In ethanol for 15h; Heating;	45%

4-fluoro-3-nitrophenylazide (28166-06-5) + C20H32N6O (140900-93-2) → C26H34N10O3 (140873-20-7)

Conditions	Yield
With sodium carbonate In ethanol for 15h; Heating;	44%

Upstream product

• 364-76-1 4-Fluoro-3-nitroaniline 

Downstream Products

• 128333-80-2 bis(1-deoxy-2,3:4,5-di-O-isopropylidene-β-D-fructopyranos-1-yl) disulfide 
• 128333-78-8 1-(4-azido-2-nitrophenyl)thio-1-deoxy-2,3:4,5-di-O-isopropylidene-β-D-fructopyranose 
• 140873-20-7 C₂₆H₃₄N₁₀O₃ 
• 140873-22-9 C₂₇H₃₆N₁₀O₃ 
• 140873-16-1 C₂₅H₃₂N₁₀O₃ 
• 140873-18-3 C₂₆H₃₄N₁₀O₃ 
• 81497-08-7 rel-(2R,6R,7S,8S)-7-butyl-8-hydroxy-2-<5-(2-nitro-4azidophenoxy)pentyl>-1-azaspiro<5.5>undecane 
• 117654-62-3 methyl (4-azido-2-nitrophenyl 5-acetamido-4,7,8,9-tetra-O-acetyl-2,3,5-trideoxy-2-thio-α-D-glycero-D-galacto-2-nonulopyranozid)onate 
• 64309-07-5 4-(2-aminoethyl)amino-3-nitro-phenylazide (napa) 
• 58775-38-5 6-(4-azido-2-nitro-phenylamino)-hexanoic acid 
• 300351-06-8 17α-[(N-4-azido-2-nitrophenyl)aminomethyl]-3,3-dimethoxy-5α-androstan-17β-ol 
• 300351-09-1 17α-[(N-4-azido-2-nitrophenyl)aminoethyl]-3,3-dimethoxy-5α-androstan-317β-ol 

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