6269-89-2

Basic information

• Product Name: 1-(4-Nitrophenyl)piperazine
• Synonyms: AKOS BBS-00003599;1-(P-NITROPHENYL)PIPERAZINE;1-NITRO-4-(1-PIPERAZINYL)BENZENE;1-(4-NITROPHENYL)PIPERAZINE;1-(4-NITRO-PHENYL)-PIPERAZINE DIHYDROCHLORIDE;1-(4-NITROPHENYL)PIPERAZINE HCL;LABOTEST-BB LT00076049;1-(4-Nitrophenyl)piperazine 97%
• CAS NO: 6269-89-2
• Molecular Formula: C₁₀H₁₃N₃O₂
• Molecular Weight: 207.23
• EINECS: 228-443-7
• Product Categories: Nitrogen cyclic compounds;Piperidines, Piperidones, Piperazines;pharmacetical;Phenyls & Phenyl-Het;Piperaizine;API intermediates;CHIRAL CHEMICALS;Phenyls & Phenyl-Het;Building Blocks;Heterocyclic Building Blocks;Piperazines
• Mol File: 6269-89-2.mol
• Article Data: 41

Chemical Properties

• Melting Point: 131-133 °C(lit.)
• Boiling Point: 346.25°C (rough estimate)
• Flash Point: 190.8 °C
• Appearance: White to beige to gray/Crystalline Powder, Crystals and/or Chunks
• Density: 1.1933 (rough estimate)
• Vapor Pressure: 2.38E-06mmHg at 25°C
• Refractive Index: 1.4830 (estimate)
• PKA: 8.68±0.10(Predicted)
• CAS DataBase Reference: 1-(4-Nitrophenyl)piperazine(CAS DataBase Reference)
• NIST Chemistry Reference: 1-(4-Nitrophenyl)piperazine(6269-89-2)
• EPA Substance Registry System: 1-(4-Nitrophenyl)piperazine(6269-89-2)

Safety Data

• Hazard Codes: Xn,Xi
• Statements: 20/21/22-36/37/38
• Safety Statements: 26-37/39-24/25-36
• RIDADR: 2811
• WGK Germany: 3
• HazardClass: 6.1
• PackingGroup: III
• Hazardous Substances Data: 6269-89-2(Hazardous Substances Data)

Usage

Chemical Properties

yellow to ochre powder

Uses

1-(4-Nitrophenyl)piperazine is a useful synthetic intermediate in the synthesis of Itraconazole (I937500); an orally active antimycotic structurally related to Ketoconazole. Also antifungal.

General Description

Inclusion interactions of 1-(4-nitrophenyl)piperazine with 4-sulfonatocalix[n]arenes were investigated by UV spectroscopy and fluorescence spectroscopy.

InChI:InChI=1/C10H13N3O2/c14-13(15)10-3-1-9(2-4-10)12-7-5-11-6-8-12/h1-4,11H,5-8H2/p+1

Synthetic route

tert-butyl 4-(4-nitrophenyl)piperazine-1-carboxylate (182618-86-6) → 1-(4-Nitrophenyl)piperazine (6269-89-2)

Conditions	Yield
With trifluoroacetic acid In dichloromethane at 20℃; for 6h;	98%
Stage #1: tert-butyl 4-(4-nitrophenyl)piperazine-1-carboxylate With Amberlyst(R) 15 In dichloromethane at 20℃; Stage #2: With ammonium hydroxide In methanol at 20℃; for 1.5h;	94%
With trifluoroacetic acid In dichloromethane at 20℃; for 1h;	90%

piperazine (110-85-0) + para-nitrophenyl bromide (586-78-7) → 1-(4-Nitrophenyl)piperazine (6269-89-2)

Conditions	Yield
With tetra-(n-butyl)ammonium iodide; potassium carbonate In dimethyl sulfoxide at 120℃; for 12h; Arylation;	98%
With potassium carbonate In N,N-dimethyl-formamide Reflux;	55%
With potassium phosphate; copper(l) iodide; ethylene glycol In isopropyl alcohol for 48h; Heating / reflux;	49.4%

piperazine (110-85-0) + 4-Fluoronitrobenzene (350-46-9) → 1-(4-Nitrophenyl)piperazine (6269-89-2)

Conditions	Yield
In N,N-dimethyl-formamide under 6000.6 Torr;	95%
In acetonitrile Reflux;	85.1%
In chloroform; acetonitrile

piperazine (110-85-0) + 4-chlorobenzonitrile (100-00-5) → 1-(4-Nitrophenyl)piperazine (6269-89-2)

Conditions	Yield
With tetra-(n-butyl)ammonium iodide; potassium carbonate In dimethyl sulfoxide at 120℃; for 12h; Arylation;	91%
With tris-(dibenzylideneacetone)dipalladium(0); 2-dicyclohexylphosphino-2′,6′-di-i-propoxy-1,1′-biphenyl; sodium t-butanolate In 1,4-dioxane at 100℃; for 0.166667h; Temperature;	86%
In diethylene glycol dimethyl ether at 100℃; for 6h;	81%

bis-(2-chloroethyl)amine hydrochloride (821-48-7) + 4-nitro-aniline (100-01-6) → 1-(4-Nitrophenyl)piperazine (6269-89-2)

Conditions	Yield
In various solvent(s) at 150℃;	90%
With potassium carbonate In butan-1-ol	16.1 g (14%)
Reflux;
With potassium iodide at 150℃; Inert atmosphere;

piperazine (110-85-0) + para-dinitrobenzene (100-25-4) → 1-(4-Nitrophenyl)piperazine (6269-89-2)

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide Arylation; Heating;	76%

bis(2-bromoethyl)amine hydrobromide (43204-63-3) + 4-nitro-aniline (100-01-6) → 1-(4-Nitrophenyl)piperazine (6269-89-2)

Conditions	Yield
With butan-1-ol

piperazine (110-85-0) + 4-chlorobenzonitrile (100-00-5) → 1-(4-Nitrophenyl)piperazine (6269-89-2) + N.N'-bis-<4-nitro-phenyl>-piperazine

Conditions	Yield
at 150℃; im Rohr;

piperazine (110-85-0) + p-nitrobenzene iodide (636-98-6) → 1-(4-Nitrophenyl)piperazine (6269-89-2)

Conditions	Yield
With potassium phosphate; copper(l) iodide In isopropyl alcohol at 20℃;

4-Fluoronitrobenzene (350-46-9) → 1-(4-Nitrophenyl)piperazine (6269-89-2)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: macroporous polymer-supported carbonate / dimethylsulfoxide / 100 °C 1.2: macroporous polymer-supported isocyanate / CH2Cl2 / 60 °C 2.1: Amberlyst(R) 15 / CH2Cl2 / 20 °C 2.2: 94 percent / aq. NH3 / methanol / 1.5 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: K2CO3 / dimethylsulfoxide / 12 h / 80 °C 2: concd. HCl / acetonitrile View Scheme
Multi-step reaction with 2 steps 1: potassium carbonate / acetonitrile / 48 h / Reflux 2: hydrogenchloride; acetic acid / water / 2 h / 20 °C View Scheme

para-nitrophenyl bromide (586-78-7) → 1-(4-Nitrophenyl)piperazine (6269-89-2)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: tri-tert-butylphosphine; palladium(II) acetate; sodium tert-butoxide / xylene / 50 °C 1.2: 100 percent / macroporous polymer-supported isocyanate / xylene / 24 h / 50 °C 2.1: Amberlyst(R) 15 / CH2Cl2 / 20 °C 2.2: 94 percent / aq. NH3 / methanol / 1.5 h / 20 °C View Scheme

1-(4-Nitrophenyl)piperazine (6269-89-2) → 4-(piperazin-1-yl)aniline (67455-41-8)

Conditions	Yield
With hydrazine hydrate at 90℃; for 1.66667h; chemoselective reaction;	100%
With palladium 10% on activated carbon In methanol at 50℃; under 37503.8 Torr;	99%
With hydrazine hydrate In water at 110℃; Sealed tube; Green chemistry;	99%

1-(4-Nitrophenyl)piperazine (6269-89-2) + 3,4-dimethoxy-benzaldehyde (120-14-9) → 1-(3,4-dimethoxybenzyl)-4-(4-nitrophenyl)piperazine (414877-58-0)

Conditions	Yield
With sodium tris(acetoxy)borohydride In dichloromethane for 18h;	100%
Stage #1: 1-(4-Nitrophenyl)piperazine; 3,4-dimethoxy-benzaldehyde With acetic acid In dichloromethane for 0.5h; Stage #2: With sodium tris(acetoxy)borohydride In dichloromethane at 20℃;	60.9%

[(1-Ethoxycyclopropyl)oxy]trimethylsilane (27374-25-0) + 1-(4-Nitrophenyl)piperazine (6269-89-2) → 1-cyclopropyl-4-(4-nitrophenyl)piperazine (700804-16-6)

Conditions	Yield
With sodium cyanoborohydride; acetic acid In methanol at 20℃; for 60h; molecular sieves;	100%
With sodium cyanoborohydride; acetic acid In methanol at 60 - 65℃; for 4h; Molecular sieve;	100%

1-(4-Nitrophenyl)piperazine (6269-89-2) + isobutyl isocyanate (1873-29-6) → 4-(4-nitrophenyl)-1-piperazinecarbothioic acid isobutylamide (412332-12-8)

Conditions	Yield
In toluene at 20℃; for 2h;	100%

1-(4-Nitrophenyl)piperazine (6269-89-2) + Ethanesulfonyl chloride (594-44-5) → 1-(ethylsulfonyl)-4-(4-nitrophenyl)piperazine (544462-63-7)

Conditions	Yield
With triethylamine In dichloromethane at 5 - 20℃; for 4h;	100%
With triethylamine In dichloromethane at 5 - 20℃; for 4h;	100%

1-(4-Nitrophenyl)piperazine (6269-89-2) + 2-chloro-5-cyano-6-ethoxy-4-phenylpyridine-3-carboxaldehyde (143815-60-5) → 3-cyano-2-ethoxy-6--5-formyl-4-phenylpyridine (151021-19-1)

Conditions	Yield
With triethylamine In tetrahydrofuran for 0.166667h; Heating;	99%

1-(4-Nitrophenyl)piperazine (6269-89-2) + 4-nitrobenzyl chloride (100-14-1) → 1-(4-nitro-benzyl)-4-(4-nitro-phenyl)-piperazine

Conditions	Yield
With silica gel for 0.0833333h; Alkylation; Microwave irradiation;	99%

potassium cyanate (590-28-3) + 1-(4-Nitrophenyl)piperazine (6269-89-2) → 4-(4-nitro-phenyl)-piperazine-1-carboxylic acid amide (63178-62-1)

Conditions	Yield
	99%

1-(4-Nitrophenyl)piperazine (6269-89-2) + ethyl bromoacetate (105-36-2) → ethyl 2-[4-(4-nitrophenyl)piperazin-1-yl]acetate (24636-99-5)

Conditions	Yield
With triethylamine In neat (no solvent) for 0.133333h; Solvent; Microwave irradiation; Green chemistry;	99%
With sodium hydrogencarbonate In acetone for 24h; Reflux;
With potassium carbonate In acetone at 20℃;

1-(4-Nitrophenyl)piperazine (6269-89-2) + N-(4-methylphenyl)-4-nitronaphthalene-1,8-dicarboximide (129-23-7) → 6-[4-(4-nitro-phenyl)-piperazin-1-yl]-2-p-tolyl-benzo[de]isoquinoline-1,3-dione

Conditions	Yield
In N,N-dimethyl acetamide for 3h; Heating;	98%

1-(4-Nitrophenyl)piperazine (6269-89-2) + (R)-trolox (53101-49-8) → (R)-3,4-dihydro-2,5,7,8-tetramethyl-2-{4-[(4-nitrophenyl)-1-piperazinyl]-carbonyl}-2H-1-benzopyran-6-ol

Conditions	Yield
Stage #1: (R)-trolox Stage #2: 1-(4-Nitrophenyl)piperazine	98%

1-(4-Nitrophenyl)piperazine (6269-89-2) + N-(9H-fluoren-2-ylmethoxycarbonyloxy)succinimide (82911-69-1) → 4-(4-nitrophenyl)piperazine-1-N-9H-fluoren-9-ylmethyloxycarbonyl

Conditions	Yield
With sodium carbonate In DMF (N,N-dimethyl-formamide); water at 0℃; for 0.333333h;	98%

di-tert-butyl dicarbonate (24424-99-5) + 1-(4-Nitrophenyl)piperazine (6269-89-2) → tert-butyl 4-(4-dimethylaminophenyl)piperazine-1-carboxylate

Conditions	Yield
With formaldehyd; palladium In ethanol; dichloromethane; ethyl acetate	98%

(1S,4R)-bicyclo[2.2.1]heptan-2-one (497-38-1, 2630-41-3) + 1-(4-Nitrophenyl)piperazine (6269-89-2) → 1-(bicyclo[2.2.1]hept-2-yl)-4-(4-nitrophenyl)piperazine (1037800-79-5)

Conditions	Yield
With sodium tris(acetoxy)borohydride; acetic acid In 1,2-dichloro-ethane at 20℃;	98%

2-chloro-4,6-dimethoxybenzenamine hydrochloride (1092069-98-1) + 1-(4-Nitrophenyl)piperazine (6269-89-2) + trichloromethyl chloroformate (503-38-8) → C19H21ClN4O5 (1092069-29-8)

Conditions	Yield
Stage #1: 2-chloro-4,6-dimethoxybenzenamine hydrochloride; trichloromethyl chloroformate With triethylamine In toluene at 60℃; for 2h; Stage #2: 1-(4-Nitrophenyl)piperazine In dichloromethane; toluene at 60 - 70℃; for 1h;	98%

1-(4-Nitrophenyl)piperazine (6269-89-2) + 4-methoxy-benzoyl chloride (100-07-2) → 1-(4-methoxybenzoyl)-4-(4-nitrophenyl)piperazine

Conditions	Yield
With triethylamine In tetrahydrofuran at 0 - 20℃; for 4h;	98%
With triethylamine In dichloromethane at 20℃;	88%

1-(4-Nitrophenyl)piperazine (6269-89-2) + 2-bromoethanol (540-51-2) → 2-(4-(4-nitrophenyl)piperazin-1-yl)ethan-1-ol (5521-38-0)

Conditions	Yield
With triethylamine In chloroform at 50℃;	97%
With triethylamine In acetone at 20℃; for 24h;	40%
With N-ethyl-N,N-diisopropylamine In acetonitrile Heating / reflux;
With N-ethyl-N,N-diisopropylamine In acetonitrile Heating / reflux;

1-(4-Nitrophenyl)piperazine (6269-89-2) + N-(5-chloro-2-nitrophenyl)acetamide (5443-33-4) → 5-(4-(4-nitrophenyl)-1-piperazinyl)-2'-nitroacetanilide (1612254-27-9)

Conditions	Yield
With triethylamine In dimethyl sulfoxide at 120℃;	97%

1-(4-Nitrophenyl)piperazine (6269-89-2) + methyl chloroformate (79-22-1) → methyl 4-(4-nitrophenyl)piperazine-1-carboxylate (91643-97-9)

Conditions	Yield
With potassium carbonate In dichloromethane at 20℃; for 0.5h;	97%
With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 0 - 20℃; for 1h;	4 g

1-(4-Nitrophenyl)piperazine (6269-89-2) + benzyl chloroformate (501-53-1) → benzyl 4-(4-nitropheny)piperazine-1-carboxylate (947673-13-4)

Conditions	Yield
With potassium carbonate In tetrahydrofuran; water for 1h; Inert atmosphere;	96.4%
With sodium hydrogencarbonate In dichloromethane; acetonitrile at 8 - 20℃; for 40h;	96%
With sodium hydrogencarbonate In dichloromethane for 21h;	93%

1-(4-Nitrophenyl)piperazine (6269-89-2) + 3-[(4-chlorobenzoyl)amino]propanoyl chloride (755024-79-4) → 4-chloro-N-[3-oxo-3-(4-(4-nitrophenyl)-1-piperazinyl)-propyl]-benzamide

Conditions	Yield
With pyridine In tetrahydrofuran at 0 - 20℃;	96.2%

1-(4-Nitrophenyl)piperazine (6269-89-2) + 3-(Trifluoromethyl)benzenesulfonyl chloride (777-44-6) → 1-(4-nitro-phenyl)-4-(3-trifluoromethyl-benzenesulfonyl)-piperazine

Conditions	Yield
With silica gel for 0.0833333h; Substitution; Microwave irradiation;	96%

1-(4-Nitrophenyl)piperazine (6269-89-2) + acrylonitrile (107-13-1) → 3-[4-(4-nitrophenyl)-piperazin-1-yl]-propionitrile (743449-17-4)

Conditions	Yield
With triethylammonium acetate at 25℃; for 0.0166667h; Aza-Michael reaction; chemoselective reaction;	96%
With multi-walled carbon nanotubes-triethylammonium hydrogen phosphate composite at 25℃; for 0.0166667h; Michael Addition; Green chemistry;	96%
With triethylamine In methanol at 20℃; for 24h;	91.04%
With single-walled carbon nanotube-triethylammonium hydrogen phosphate ionic liquid at 25℃; for 0.0166667h; Reagent/catalyst;	97 %Chromat.

dichloroacethyl chloride (79-36-7) + 1-(4-Nitrophenyl)piperazine (6269-89-2) → 2,2-dichloro-1-(4-(4-nitrophenyl)piperazine-1-yl)ethan-1-one (77367-94-3)

Conditions	Yield
for 4h;	96%
With triethylamine In water; toluene

1-(4-Nitrophenyl)piperazine (6269-89-2) + propargyl bromide (106-96-7) → N-(4-nitrophenyl)-N'-propargylpiperazine (72955-80-7)

Conditions	Yield
With potassium carbonate In acetonitrile at 60℃; for 18h; Inert atmosphere;	95.4%
With pyridine; potassium carbonate In ethyl acetate at 25℃; for 4h; Cooling with ice;
With potassium carbonate In ethyl acetate at 20℃;
With potassium carbonate In dichloromethane at 0 - 20℃; for 5h;

1-(4-Nitrophenyl)piperazine (6269-89-2) + chloroacetyl chloride (79-04-9) → 2-chloro-1-<4-(4-nitrophenyl)piperazin-1-yl>acetamide (16264-11-2)

Conditions	Yield
With calcium carbonate In butanone Ambient temperature;	95%
With triethylamine In dichloromethane at 0 - 20℃; for 3h;	92%

formaldehyd (50-00-0) + tetrahydropyrrolo[1,2-c]imidazol-1,3-dione (5768-79-6) + 1-(4-Nitrophenyl)piperazine (6269-89-2) → 2-[4-(4-Nitro-phenyl)-piperazin-1-ylmethyl]-tetrahydro-pyrrolo[1,2-c]imidazole-1,3-dione

Conditions	Yield
In ethanol at 100℃;	95%

1-(4-Nitrophenyl)piperazine (6269-89-2) + ammonium formate (16712-16-6, 64165-14-6, 65387-22-6, 70179-79-2, 540-69-2) → 4-(4-nitrophenyl)piperazine-1-carbaldehyde (321898-63-9)

Conditions	Yield
In acetonitrile for 7.5h; Formylation;	95%

Upstream product

• 43204-63-3 bis(2-bromoethyl)amine hydrobromide 
• 100-01-6 4-nitro-aniline 
• 110-85-0 piperazine 
• 100-00-5 4-chlorobenzonitrile 
• 350-46-9 4-Fluoronitrobenzene 
• 586-78-7 para-nitrophenyl bromide 
• 636-98-6 p-nitrobenzene iodide 
• 821-48-7 bis-(2-chloroethyl)amine hydrochloride 
• 100-25-4 para-dinitrobenzene 
• 182618-86-6 tert-butyl 4-(4-nitrophenyl)piperazine-1-carboxylate 

Downstream Products

• 136603-21-9 [4-(2-Phenyl-[1,8]naphthyridine-3-carbonyl)-phenoxy]-acetic acid [1-[4-(4-nitro-phenyl)-piperazin-1-ylmethyl]-2-oxo-1,2-dihydro-indol-(3Z)-ylidene]-hydrazide 
• 128375-66-6 C₂₇H₃₄N₆O₄ 
• 94011-97-9 4-(5-Chloro-2-hydroxybenzoyl)-1-(4-nitrophenyl)piperazine 
• 94011-99-1 (3,5-Dibromo-2-hydroxy-phenyl)-[4-(4-nitro-phenyl)-piperazin-1-yl]-methanone 
• 16264-08-7 1-[4-(4-Nitro-phenyl)-piperazinyl]-ethanone 
• 103377-69-1 N-(5,11-Dihydro-10-thia-dibenzo[a,d]cyclohepten-5-yl)-4-[4-(4-nitro-phenyl)-piperazin-1-yl]-butyramide 
• 94011-98-0 (5-Bromo-2-hydroxy-phenyl)-[4-(4-nitro-phenyl)-piperazin-1-yl]-methanone 
• 93065-60-2 (4-nitrophenyl)(4-(4-nitrophenyl)piperazin-1-yl)methanone 
• 103247-15-0 N-(7-Hydroxy-2,2,4,6-tetramethyl-indan-1-yl)-2-[4-(4-nitro-phenyl)-piperazin-1-yl]-acetamide 
• 127625-54-1 2-<3-<4-(4-nitrophenyl)-1-piperazinyl>propyl>-2H-naphth<1,8-cd>isothiazole 1,1-dioxide 
• 151021-19-1 3-cyano-2-ethoxy-6--5-formyl-4-phenylpyridine 
• 103076-84-2 2-{2-[4-(4-Nitro-phenyl)-piperazin-1-yl]-ethoxy}-benzaldehyde 
• 136497-67-1 1-(p-nitrophenyl)-4-(1-p-methoxyphenyl-2-methyl)propylpiperazine 
• 136497-66-0 2-methyl-1-(4-methylphenyl)-1-<4-(4-nitrophenyl)piperazin-1-yl>propane 

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