6531-38-0

Basic information

• Product Name: Piperazine-1,4-diethylamine
• Synonyms: piperazine-1,4-diethylamine;1,4-Piperazinediethanamine;1,4-Piperazinediethanamine(9CI);2,2''-PIPERAZINE-1,4-DIYLDIETHANAMINE;N,N''-DI-(2-AMINOETHYL)PIPERAZINE;1,4-Bis(2-aminoethyl)piperazine;1,4-Piperazinediethaneamine;2-[4-(2-Aminoethyl)piperazin-1-yl]ethylamine
• CAS NO: 6531-38-0
• Molecular Formula: C₈H₂₀N₄
• Molecular Weight: 172.27
• EINECS: 229-428-8
• Product Categories: PIPERIDINE
• Mol File: 6531-38-0.mol
• Article Data: 13

Chemical Properties

• Melting Point: 40 °C
• Boiling Point: 302.2 °C at 760 mmHg
• Flash Point: 151.4 °C
• Appearance: /
• Density: 1.006g/cm³
• Vapor Pressure: 0.00101mmHg at 25°C
• Refractive Index: 1.511
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• PKA: 10.41±0.10(Predicted)
• CAS DataBase Reference: Piperazine-1,4-diethylamine(CAS DataBase Reference)
• NIST Chemistry Reference: Piperazine-1,4-diethylamine(6531-38-0)
• EPA Substance Registry System: Piperazine-1,4-diethylamine(6531-38-0)

Safety Data

• RIDADR: 1760
• HazardClass: 8
• PackingGroup: II
• Hazardous Substances Data: 6531-38-0(Hazardous Substances Data)

Usage

General Description

Piperazine-1,4-diethylamine, also known as 1,4-bis(2-ethylhexyl)piperazine, is a chemical compound that is often used in the synthesis of other chemicals, including pharmaceutical products. It has a molecular formula of C14H32N2 and it exists in a liquid state at room temperature. Piperazine-1,4-diethylamine is colorless, possesses a mild odor, and is soluble in most organic solvents. It should be handled with care as it is corrosive and can cause significant eye, skin, and respiratory irritation. It may also have harmful effects if swallowed or inhaled.

InChI:InChI=1/C8H20N4/c9-1-3-11-5-7-12(4-2-10)8-6-11/h1-10H2

Synthetic route

2‐[4‐(cyanomethyl)piperazin‐1‐yl]acetonitrile (5623-99-4) → 1,4-bis(2-aminoethyl)piperazine (6531-38-0)

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran for 4h; Reflux;	87%
Stage #1: 2‐[4‐(cyanomethyl)piperazin‐1‐yl]acetonitrile With lithium aluminium tetrahydride In tetrahydrofuran for 3h; Heating / reflux; Stage #2: With potassium hydroxide In tetrahydrofuran; water	80%
With ammonia; hydrogen; nickel In ethanol at 20℃;	73%

N,N'-bis(2-phthalimidoethyl)piperazine (20541-87-1) → 1,4-bis(2-aminoethyl)piperazine (6531-38-0)

Conditions	Yield
With potassium hydroxide; sodium hydroxide at 300 - 330℃;	75%
With hydrogenchloride at 130℃; im Rohr;
With hydrazine hydrate
With hydrazine

ethyleneimine (151-56-4) + aminoethylpiperazine (140-31-8) → 1,4-bis(2-aminoethyl)piperazine (6531-38-0) + 1-<2-(2-aminoethyl)aminoethyl>piperazine (24028-46-4)

Conditions	Yield
With hydrogenchloride In water at 50℃;	A 79.5 % Chromat. B 20.5 % Chromat.
With hydrogenchloride In water at 25℃; Kinetics; Thermodynamic data; acid-catalyzed ring opening reactions at various temperature, Ea, ΔH are given;
With hydrogenchloride In water at 40℃;	A 80.0 % Chromat. B 20.0 % Chromat.

piperazine-N.N'-diacetic acid dinitrile → 1,4-bis(2-aminoethyl)piperazine (6531-38-0)

Conditions	Yield
With ethanol; sodium

Glyoxal (131543-46-9) + triethylentetramine (112-24-3) → 1,4-bis(2-aminoethyl)piperazine (6531-38-0)

Conditions	Yield
With sodium tetrahydroborate In ethanol at -10℃; for 2h;
With sodium tetrahydroborate
With sodium tetrahydroborate In ethanol at 0℃; for 2h;

N,N'-Bis(2-phthalimidoethyl)ethylene diamine (84429-08-3) → 1,4-bis(2-aminoethyl)piperazine (6531-38-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 61 percent / potassium carbonate / 0.17 h / 132 °C 2: 75 percent / aq.sodium hydroxide, potassium hydroxide / 300 - 330 °C View Scheme

triethylentetramine (112-24-3) → 1,4-bis(2-aminoethyl)piperazine (6531-38-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: 65 percent / 195 °C 2: 61 percent / potassium carbonate / 0.17 h / 132 °C 3: 75 percent / aq.sodium hydroxide, potassium hydroxide / 300 - 330 °C View Scheme

1,4-bis(2-aminoethyl)piperazine (6531-38-0) + C15H11NO3 → C38H38N6O4

Conditions	Yield
In ethanol at 80℃; for 8h;	92%

1,4-bis(2-aminoethyl)piperazine (6531-38-0) + nickel(II) perchlorate hexahydrate → (3-[4-(3-aminopropyl)-piperazin-1-yl]-propylamine)nickel(II) perchlorate

Conditions	Yield
In methanol refluxed for 2 h; ppt. filtered, washed with cold MeOH, dried; elem. anal.;	90%

1,4-bis(2-aminoethyl)piperazine (6531-38-0) + 3,5-di-tert-butyl-2-hydroxybenzaldehyde (37942-07-7) → N,N'-bis{2-[(2-ethylimino)methyl]-4,6-di-tert-butylphenol}piperazine

Conditions	Yield
In ethanol for 3h; Reflux;	87%

1,4-bis(2-aminoethyl)piperazine (6531-38-0) + salicylaldehyde (90-02-8) → 1,4-bis(2-salicylideneaminoethyl)piperazine (80744-39-4)

Conditions	Yield
In methanol for 3h; Cooling with ice;	87%

thiophene-2-carbaldehyde (98-03-3) + 1,4-bis(2-aminoethyl)piperazine (6531-38-0) → N,N'-bis[2-(thiophen-2-ylmethyleneamino)ethyl]piperazine (1207281-39-7)

Conditions	Yield
In ethanol for 3h; Reflux;	86%

1,4-bis(2-aminoethyl)piperazine (6531-38-0) + 5-bromosalicyclaldehyde (1761-61-1) → N,N'-bis{2-[(2-ethylimino)methyl]-5-bromophenol}piperazine (1207281-37-5)

Conditions	Yield
In ethanol for 3h; Reflux;	85%

1,4-bis(2-aminoethyl)piperazine (6531-38-0) + phthalic anhydride (85-44-9) → N,N'-bis(2-phthalimidoethyl)piperazine (20541-87-1)

Conditions	Yield
In acetic acid Condensation; Heating;	80%

pyridine-2-carbaldehyde (1121-60-4) + 1,4-bis(2-aminoethyl)piperazine (6531-38-0) → N-((1-pyridin-2-yl)formylidene)-N'-[2-(4-[2-[((1-pyridin-2-yl)formylidene)amino]ethyl]piperazin-1-yl)ethyl]amine (917590-68-2)

Conditions	Yield
In ethanol for 3h; Reflux;	80%

1,4-bis(2-aminoethyl)piperazine (6531-38-0) + salicylaldehyde (90-02-8) → N,N'-bis{2-[(2-ethylimino)methyl]phenol}piperazine (78186-31-9)

Conditions	Yield
In ethanol for 3h; Reflux;	80%
In methanol for 3h; Cooling with ice;

1,4-bis(2-aminoethyl)piperazine (6531-38-0) + phenyl(pyridin-2-yl)methanone (91-02-1) → N-((1-pyridin-2-yl)benzylidene)-N'-[2-(4-[2-[((1-pyridin-2-yl)benzylidene)amino]ethyl]piperazin-1-yl)-ethyl]amine (959850-48-7)

Conditions	Yield
for 7h; Reflux;	79.1%

1,4-bis(2-aminoethyl)piperazine (6531-38-0) + 9-methylphenazine-1-carboxylic acid imidazolide (343247-31-4) → C36H36N8O2

Conditions	Yield
In tetrahydrofuran at 20℃;	77%

1,4-bis(2-aminoethyl)piperazine (6531-38-0) + 4,7-dichloroquinoline (86-98-6) → N-(2-(4-(2-aminoethyl)piperazin-1-yl)ethyl)-7-chloroquinolin-4-amine (1416359-97-1)

Conditions	Yield
In neat (no solvent) at 80 - 125℃; for 3h;	76%

1,4-bis(2-aminoethyl)piperazine (6531-38-0) + 3-nitro-1,8-naphthalic anhydride (3027-38-1) → C32H26N6O8 (500865-45-2)

Conditions	Yield
In ethanol; toluene for 4h; Reflux;	73%

1,4-bis(2-aminoethyl)piperazine (6531-38-0) + 3‐acetyl‐2‐hydroxy‐6‐methyl‐4H‐pyran‐4‐one (16807-48-0) → ((3E,3'E)-3,3'-(((piperazine-1,4-diylbis(ethane-2,1-diyl))bis(azanediyl))bis(ethan1-yl-1-ylidene))bis(6-methyl-2H-pyran-2,4(3H)-dione))

Conditions	Yield
In ethanol for 24h;	63%

1,4-bis(2-aminoethyl)piperazine (6531-38-0) + 5-((Z)-4-hydroxybenzylidene)-2-methylmercapto-4-thiazolidinone (521973-02-4) → (5Z,5'Z)-2,2'-[piperazine-1,4-diylbis(ethane-2,1-diylimino)]bis(5-(4-hydroxybenzylidene)-1,3-thiazol-4(5H)-one) (1415582-35-2)

Conditions	Yield
In ethanol for 8h; Reflux;	58%

1,4-bis(2-aminoethyl)piperazine (6531-38-0) + 9-Chloro-N-<2-(dimethylamino)ethyl>acridine-4-carboxamide (89459-23-4) → C44H54N10O2

Conditions	Yield
In phenol at 125℃; for 2h;	48%

1,4-bis(2-aminoethyl)piperazine (6531-38-0) + p-benzyloxybenzenesulfonyl chloride (87001-32-9) → N,N'-(2,2'-(piperazine-1,4-diyl)bis(ethane-2,1-diyl))bis(4-(benzyloxy)benzenesulfonamide)

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 2h;	47%

pyridine-2-carbaldehyde (1121-60-4) + 1,4-bis(2-aminoethyl)piperazine (6531-38-0) + cobalt(II) perchlorate hexahydrate → CoBrC4H8N2(CH2CH2NCHC5H4N)2(1+)*ClO4(1-)=CoBrC4H8N2(CH2CH2NCHC5H4N)2ClO4

Conditions	Yield
With NaOH In methanol abs. MeOH soln. of NaOH added to abs. MeOH soln. of piperazine deriv.; stirred at room temp. for a few min; filtered off; washed with abs. MeOH;added dropwise to hot abs. MeOH soln. of Co(ClO4)2, and py-2-CHO over a period of 1 h; refluxed for 18 h; concd.; pptd. by addn. of Et2O; filtered; washed with cold Et2O; dried; elem. anal.;	43%

1,4-bis(2-aminoethyl)piperazine (6531-38-0) + N-(N-methylpiperidin-4-yl)-9-chloroacridine-4-carboxamide (1030022-78-6) → N,N-bis{4-[N-(N-methylpiperidin-4-yl)carbamoyl]acridin-9-yl}-[1,4-bis(2-aminoethyl)-piperazine] (1030022-76-4)

Conditions	Yield
In phenol at 125℃; for 2h;	35%

1,4-bis(2-aminoethyl)piperazine (6531-38-0) + N-[2-(4-morpholinyl)ethyl]-9-chloroacridine-4-carboxamide (646072-61-9) → C48H58N10O4

Conditions	Yield
In phenol at 125℃; for 2h;	31%

1,4-bis(2-aminoethyl)piperazine (6531-38-0) + 3-(butylamino)-5-(1H-imidazole-1-carbonyl)-2-phenoxybenzenesulfonamide (1021869-65-7) → C25H38N6O4S (1021869-54-4)

Conditions	Yield
In dichloromethane at 25℃; under 760.051 Torr;	20.46%

1,4-bis(2-aminoethyl)piperazine (6531-38-0) + formaldehyd (50-00-0) + β-naphthol (135-19-3) → (13,13'-piperazine-(N,N,N''',N'''-tetra((2-hydroxynaphthyl)methyl))ethane)amine

Conditions	Yield
In methanol; water for 0.5h; Condensation;	13%

1,4-bis(2-aminoethyl)piperazine (6531-38-0) + ethyl (2E)‐2‐(hydroxyimino)acetate (31767-15-4) → (2E)-2-(N-hydroxyimino)-N-[2-(4-{2-[(2E)-2-(N-hydroxyimino)acetamido]ethyl}piperazin-1-yl)ethyl]acetamide

Conditions	Yield
In ethanol at 90℃; for 48h;	10%

1,4-bis(2-aminoethyl)piperazine (6531-38-0) + 4-bromo-6-methoxy-2-methylquinoline (856095-00-6) → 1-(2-amino-ethyl)-4-[2-(6-methoxy-2-methyl-[4]quinolylamino)-ethyl]-piperazine + 1,4-bis-[2-(6-methoxy-2-methyl-[4]quinolylamino)-ethyl]-piperazine

Conditions	Yield
at 170℃;

1,4-bis(2-aminoethyl)piperazine (6531-38-0) + 4-bromo-6-methoxy-2-methylquinoline (856095-00-6) → 1,4-bis-[2-(6-methoxy-2-methyl-[4]quinolylamino)-ethyl]-piperazine

Conditions	Yield
at 160℃;

1,4-bis(2-aminoethyl)piperazine (6531-38-0) → 1,4-bis-(2-isocyano-ethyl)-piperazine

Conditions	Yield
With sodium hydroxide; chloroform

1,4-bis(2-aminoethyl)piperazine (6531-38-0) + 9-Chloroacridine (1207-69-8) → C34H34N6 (97614-83-0)

Conditions	Yield
With phenol at 100℃;

Upstream product

• 20541-87-1 N,N'-bis(2-phthalimidoethyl)piperazine 
• 151-56-4 ethyleneimine 
• 140-31-8 aminoethylpiperazine 
• 112-24-3 triethylentetramine 
• 84429-08-3 N,N'-Bis(2-phthalimidoethyl)ethylene diamine 
• 131543-46-9 Glyoxal 
• 5623-99-4 2‐[4‐(cyanomethyl)piperazin‐1‐yl]acetonitrile 

Downstream Products

• 20541-87-1 N,N'-bis(2-phthalimidoethyl)piperazine 
• 78186-31-9 N,N'-bis{2-[(2-ethylimino)methyl]phenol}piperazine 
• 1207281-37-5 N,N'-bis{2-[(2-ethylimino)methyl]-5-bromophenol}piperazine 
• 959850-48-7 N-((1-pyridin-2-yl)benzylidene)-N'-[2-(4-[2-[((1-pyridin-2-yl)benzylidene)amino]ethyl]piperazin-1-yl)-ethyl]amine 
• 1416360-00-3 C₃₀H₃₃ClF₃N₅O₂S 
• 1415582-35-2 (5Z,5'Z)-2,2'-[piperazine-1,4-diylbis(ethane-2,1-diylimino)]bis(5-(4-hydroxybenzylidene)-1,3-thiazol-4(5H)-one) 
• 80744-39-4 1,4-bis(2-salicylideneaminoethyl)piperazine 
• 1021869-54-4 C₂₅H₃₈N₆O₄S 

Relevant articles and documents

Bis-aminals of linear tetraamines: Kinetic and thermodynamic aspects of the condensation reaction

The kinetic and thermodynamic aspects of the condensation reaction of dicarbonyl compounds with linear tetraamines were examined in the light of identification of intermediates and DFT calculations. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, German

Syntheses and crystal structures of Ni(II) complexes with pyridine-based macrocyclic ligands

Three pyridine-based macrocyclic ligands, two containing one pyridine pendant arm (L1 and L2) and one containing piperazine rings in the macrocyclic scaffold (L3), with an increasing size of the macrocycle from 12-, 14- to 30-membered ring for L1–L3 were synthesized and characterized. A series of Ni(II) complexes with all these ligands, with molecular formulas [NiL1(CH3OH)](ClO4)2 (1), [NiL2(CH3CN)](ClO4)2 (2), and [Ni2L3(DMF)2(CH3CN)2](ClO4)4 (3) (DMF = N,N–dimethylformamide), was prepared and thoroughly characterized. Single crystal X-ray structural analysis confirmed that all the complexes have a coordination number of six and their geometries are close to octahedral. In the case of the mononuclear complexes 1 and 2, all the nitrogen atoms of the macrocycle are coordinated, however, in the dinuclear complex 3 with the piperazine-based ligand L3, two nitrogen donor atoms (of the total number of ten) are uncoordinated. The first coordination spheres of all the complexes are completed by solvent molecules. The values of effective magnetic moments, determined by the Evans method in solution, are 3.12, 3.19 and 4.36 μB for complexes 1, 2 and 3, respectively, which correspond well to the theoretical spin-only values.

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