PRODUCTS

TRIETHYLENETETRAMINE

Triethylenetetramine (TETA and trien), also known as trientine (INN) when used medically, is an organic compound with the formula [CH2NHCH2CH2NH2]2.
The pure freebase is a colorless oily liquid, but, like many amines, older samples assume a yellowish color due to impurities resulting from air-oxidation.
Triethylenetetramine is soluble in polar solvents.
The branched isomer tris(2-aminoethyl)amine and piperazine derivatives may also be present in commercial samples of Triethylenetetramine.
The hydrochloride salts are used medically as a treatment for copper toxicity.

CAS: 112-24-3
European Community (EC) Number: 203-950-6

IUPAC Name: N'-[2-(2-aminoethylamino)ethyl]ethane-1,2-diamine

Molecular Weight: 146.23 g/mol
Molecular Formula: C6H18N4

TRIETHYLENETETRAMINE, trientine, 112-24-3, Trien, Triethylene tetramine, Tecza, TETA, 1,2-Ethanediamine, N,N'-bis(2-aminoethyl)-, DEH 24, Araldite hardener HY 951, Araldite HY 951, 1,4,7,10-Tetraazadecane, 1,8-Diamino-3,6-diazaoctane, Trientina, Trientinum, triethylene tetraamine, N,N'-Bis(2-aminoethyl)-1,2-ethanediamine, Trethylenetetramine, 3,6-Diazaoctane-1,8-diamine, N,N'-Bis(2-aminoethyl)ethylenediamine, triethylenetetraamine, NSC 443, Syprine, 2,2,2-tetramine, HY 951, N,N'-bis(2-aminoethyl)ethane-1,2-diamine, CCRIS 6279, HSDB 1002, Trientinum [INN-Latin], NSC-443, Trientina [INN-Spanish], Ethylenediamine, N,N'-bis(2-aminoethyl)-, N'-[2-(2-aminoethylamino)ethyl]ethane-1,2-diamine, EINECS 203-950-6, UNII-SJ76Y07H5F, MFCD00008169, Trientine [INN], BRN 0605448, SJ76Y07H5F, DTXSID9023702, CHEBI:39501, AI3-24384, N,N-Bis(2-aminoethyl)-1,2-diaminoethane, EPH 925, Tomography, x-ray computed trientine, CHEMBL609, (2-aminoethyl)({2-[(2-aminoethyl)amino]ethyl})amine, DTXCID503702, 4-04-00-01242 (Beilstein Handbook Reference), NCGC00091695-01, NCGC00091695-03, Trientinum (INN-Latin), N,N'-Bis(2-aminoethyl)-1,2-diaminoethane, Trientina (INN-Spanish), 1,2-Ethanediamine, N1,N2-bis(2-aminoethyl)-, N1,N1'-(Ethane-1,2-diyl)diethane-1,2-diamine, Triethylenetetramine (Technical Grade), CAS-112-24-3, Rutapox VE 2896, UN2259, RT 1AX, TETA (crosslinking agent), triene, Trientene, 1,6-diazaocane, 3,8-diamine, VE 2896, TRIENTINE [MI], 1,7,10-Tetraazadecane, TRIENTINE [VANDF], N1,N2-Bis(2-aminoethyl)-1,2-ethanediamine, bmse000773, Texlin300 (Salt/Mix), TRIENTINE [WHO-DD], 3,6-Diazaoctanethylenediamin, SCHEMBL15439, WLN: Z2M2M2Z, BIDD:ER0303, BIDD:GT0014, NSC443, SCHEMBL6423840, A16AX12, TRIETHYLENETETRAMINE [HSDB], n,n'-bis(aminoethyl)ethylenediamine, STR03562, n,n'-bis(2-aminoethyl)ethanediamine, Tox21_111162, Tox21_201066, BDBM50323751, STL477736, N,N'-Di(2-aminoethyl)ethylenediamine, AKOS006223906, ethane, 1,2-bis(2-aminoethyl)amino-, ethane, 1,2-bis(2-aminoethylamino)-, Tox21_111162_1, Triethylenetetramine, >=97.0% (T), DB06824, Ethylenediamine,N'-bis(2-aminoethyl)-, NCGC00091695-04, NCGC00258619-01, BP-30180, Ethanediamine, N,N'-bis(2-aminoethyl)-, SBI-0206814.P001, DB-041060, Triethylenetetramine, technical grade, 60%, NS00001757, T0429, Triethylenetetramine [UN2259] [Corrosive], C07166, EN300-651158, N,N'-BIS-(2-AMINOETHYL)ETHYLENEDIAMINE, AB00573244_07, N,N''-Bis-(2-amino-ethyl)-ethane-1,2-diamine, Q418386, J-018026, N,N''-BIS(2-AMINOETHYL)-1,2-ETHANEDIAMINE, W-109064, 105821-86-1

Triethylenetetramine (TETA) is an organic compound with the chemical formula C6H18N4.
Triethylenetetramine is a derivative of ethylenediamine, an amino-functional alkane.
Therefore, Triethylenetetramine is obtained from the reaction of ethylenediamine and ammonia.

Triethylenetetramine is a versatile chemical used in various industries.
Triethylenetetramine serves as a cross-linking agent in resin, paint, and ink production.
Additionally, Triethylenetetramine’s used as a catalyst in petroleum refineries, a flocculation agent in water treatment, a surfactant in metal processing, and a corrosion inhibitor.

Triethylenetetramine (TETA) is a colorless to light-yellow liquid containing linear, branched and cyclic molecules.
Triethylenetetramine is mainly used in the manufacture of fuel oil additives, lubricating oil additives and epoxy curing agents.
Triethylenetetramine is also used in the production of asphalt additives.

Triethylenetetramine is a glycol ester that has the chemical formula C6H14N4O2.
Triethylenetetramine is soluble in water and has high adsorption capacity.
Triethylenetetramine is used as an inhibitor molecule in reactions, where it prevents the formation of other molecules by reacting with the reactants.
The inhibition reaction can be reversed by adding a suitable base or acid to the solution.
Triethylenetetramine can be used in a model system to study redox potentials because it can be titrated and studied in detail using calorimetry or plasma mass spectrometry.

Triethylenetetramine is a mixture of four TETA ethyleneamines with close boiling points including linear, branched and two cyclic molecules.

Triethylenetetramine (TETA) is triethylenetetramine.
Triethylenetetramine acts as curing agent for epoxy resins.
Triethylenetetramine also functions as a corrosion inhibitor, surfactant and mineral processing aid.
Triethylenetetramine is suitable for sealants.
Triethylenetetramine (TETA) is used to produce thermoplastic polyamide resins for hot-melt adhesives.
The shelf life of the product is 24 months.

Triethylenetatramine (TETA), also known as trientine, is a potent and selective copper (II)-selective chelator.
Triethylenetetramine is a structural analog of linear polyamine compounds, spermidine and spermine.
Triethylenetetramine was first developed in Germany in 1861 and its chelating properties were first recognized in 1925.
Initially approved by the FDA in 1985 as a second-line treatment for Wilson's disease, Triethylenetetramine is currently indicated to treat adults with stable Wilson’s disease who are de-coppered and tolerant to penicillamine.

Triethylenetetramine (TETA and trien), also known as trientine (INN) when used medically, is an organic compound with the formula [CH2NHCH2CH2NH2]2.
The pure freebase is a colorless oily liquid, but, like many amines, older samples assume a yellowish color due to impurities resulting from air-oxidation.
Triethylenetetramine is soluble in polar solvents.
The branched isomer tris(2-aminoethyl)amine and piperazine derivatives may also be present in commercial samples of TETA.
The hydrochloride salts are used medically as a treatment for copper toxicity.

Triethylenetetramine has been used as an additive to enhance the peak resolution ability of capillary zone electrophoresis (CZE) running buffer system to separate and quantitate the monoclonal antibodies by the CZE method.
Triethylenetetramine may be used for the amination of polyacrylonitrile fibers to form novel fiber catalysts for Knoevenagel condensation in aqueous media.
Triethylenetetramine also acts as a copper (II)-selective chelator.
Triethylenetetramine may also be used as a growth-orientator in the formation of 1D zinc sulfide nanoarchitectures.

2,2,2-tetramine is a polyazaalkane that is decane in which the carbon atoms at positions 1, 4, 7 and 10 are replaced by nitrogens.
Triethylenetetramine has a role as a copper chelator.
Triethylenetetramine is a tetramine and a polyazaalkane.

Triethylenetatramine (TETA), also known as trientine, is a potent and selective copper (II)-selective chelator.
Triethylenetetramine is a structural analog of linear polyamine compounds, [spermidine] and [spermine].
Triethylenetetramine was first developed in Germany in 1861 and its chelating properties were first recognized in 1925.
Initially approved by the FDA in 1985 as a second-line treatment for Wilson's disease, Triethylenetetramine is currently indicated to treat adults with stable Wilson’s disease who are de-coppered and tolerant to [penicillamine].
Triethylenetetramine has been investigated in clinical trials for the treatment of heart failure in patients with diabetes.

Triethylenetetramine is a compound that functions as a chelating agent in experimental applications.
Triethylenetetramine acts by forming coordination complexes with metal ions, particularly copper, in a process known as chelation.
Has the ability to bind to metal ions through multiple sites, effectively sequestering them and preventing their participation in various chemical reactions.
In this way, triethylenetetramine can be used to remove metal ions from solutions or to inhibit metal-catalyzed reactions in experimental systems.
Triethylenetetramine's mode of action involves the formation of stable, water-soluble complexes with metal ions, thereby altering reactivity of the system.
Chelating properties make it a useful for studying metal ion-dependent processes in experimental, as it can effectively modulate the availability and activity of metal ions in a controlled manner.

Triethylenetetramine is used in synthesis of detergents, softeners, and dyestuffs;
manufacture of pharmaceuticals;
vulcanization accelerator of rubber;
thermo setting resin;
epoxy curing agent;
lubricating-oil additive;
analytical reagent for Cu, Ni;
chelating agent;
treatment of Wilson's disease.

Triethylenetetramine (TETA) is hygroscopic, corrosive, and has a strong ammoniacal odor.
With water a crystalline hydrate is formed.
Like DETA, Triethylenetetramine is completely miscible with water and many polar organic solvents, but less so with lipids; with CCl4 a violent reaction occurs.
Triethylenetetramine's four pKa values are 3.32, 6.67, 9.20, and 9.92.
Technical-grade Triethylenetetramine is sometimes available as a distillation cut that also contains branched isomers and cyclic compounds.

The linear polyamine triethylenetetramine is a high–boiling point, oily liquid that was first prepared in 1890 by A. W. von Hoffmann.
He built on the synthesis of ethylenediamine by using condensation reactions between chloramines.
Today, triethylenetetramine is made by heating ethylenediamine or ethanolamine with ammonia and then separating it from the product mixture.

Triethylenetetramine’s primary commercial use is curing epoxy resins.
Triethylenetetramine is also used in analytical procedures for determining nickel and copper; it is a lubricating oil additive; and in medicine, along with penicillamine, it is used to remove copper from the body as a treatment for Wilson’s disease.

Triethylenetetramine – TETA is an oily liquid.
Triethylenetetramine is colourless. However, like many amines, its older samples have the appearance of a yellow-coloured liquid because of impurities resulting from air oxidation.
Triethylenetetramine is a slightly viscous liquid.
Triethylenetetramine is soluble in polar solvents.
Triethylenetetramine is slightly less dense than water.
Triethylenetetramine is combustible but difficult to ignite.
Triethylenetetramine is corrosive to metals and tissue.
Triethylenetetramine's vapours are heavier than air.
Triethylenetetramine has a fishy or ammoniacal odour.
Triethylenetetramine is soluble in water.

Chemical Applications and Strengths

Triethylenetetramine – TETA is an extremely useful chemical compound and therefore, has many industrial applications.
Triethylenetetramine's main applications and strengths are:

- Triethylenetetramine – TETA is most commonly used as a crosslinker or hardener in epoxy curing.

- Triethylenetetramine's hydrochloride salt which is known as trientine hydrochloride is a chelating agent.
This salt is used to bind and remove copper in the body to treat Wilson’s disease.
Triethylenetetramine therapy is an effective starting therapy.
- Triethylenetetramine is used in the manufacturing of cleaning products such as detergents.
- In the pharmaceutical industries, Triethylenetetramine is used for the production of pharmaceuticals.
- Triethylenetetramine is consumed for the production of many chemicals in the chemical industries
- In medicine Triethylenetetramine is used as a replacement of D-penicillamine.
- Triethylenetetramine is utilised for the casting and surface treatment of metals.
- Triethylenetetramine is effective in the production of water softeners.
- Triethylenetetramine is employed in products used in the process of collection, purification, and distribution of water.

Industries Using Triethylenetetramine (TETA):

Triethylenetetramine finds versatile use across various industries, including:

Chemical industry: Triethylenetetramine is used in the production of various chemicals such as resins, varnishes, and paints.

Oil industry: Triethylenetetramine serves as an intermediate for lubrication, emulsion stabilization, and formulation of oil products.

Mining industry: Triethylenetetramine is used as a frothing agent in mineral flotation.

Pharmaceutical industry: Triethylenetetramine is used as an intermediate in the production of certain drugs.

Water treatment industry: Triethylenetetramine is utilized for heavy metal removal and water softening in water treatment processes.

Other industries: Triethylenetetramine is also used in the paper, textile, and rubber industries.

Triethylenetetramine’s widespread applications have established it as a common chemical in various industries.

TRIETHYLENETETRAMINE is a mixture of four TETA ethyleneamines with close boiling points including linear, branched and two cyclic molecules.

Triethylenetetramine is used for asphalt additives, mineral processing aids, corrosion inhibitors, polyamide resins, epoxy curing agents, surfactants, hydrocarbon purification, textile additives, lube oil and fuel additives.

Applications
Catalyzes the hydrolysis of N-terminal peptide bonds.
Determination of the cation exchange capacity (CEC) of clay minerals is by using the complexes of copper(II) ion with triethylenetetramine and tetraethylenepentamine.
Variable spin iron(iii) chelates with hexadentate ligands are derived from triethylenetetramine and various salicylaldehydes.
Adsorption of Cu(II), Cd(II) and Pb(II) from aqueous single metal solutions by succinylated twice-mercerized sugarcane bagasse functionalized with triethylenetetramine.

Experimental Properties

Physical Description: Triethylenetetramine appears as a yellowish liquid.
Less dense than water.
Combustible, though may be difficult to ignite.
Corrosive to metals and tissue.
Vapors heavier than air.
Toxic oxides of nitrogen produced during combustion.
Used in detergents and in the synthesis of dyes, pharmaceuticals and other chemicals.
Color / Form: MODERATELY VISCOUS, YELLOWISH LIQUID
Boiling Point: 511 to 513 °F at 760 mmHg
Melting Point: 54 °F
Flash Point: 275 °F
Solubility: greater than or equal to 100 mg/mL at 68.4 °F
Density: 0.982 at 68 °F
Vapor Density: 5.04 (AIR= 1)
Vapor Pressure: less than 0.01 mmHg at 68 °F
LogP: -1.4/-1.66
Stability / Shelf Life: VOLATILE
Autoignition Temperature: 640 °F
Viscosity: 27.24 mm²/s at 20 °C
pH: STRONGLY BASIC (PH 10 IN 1% AQ SOLN)
Refractive Index: INDEX OF REFRACTION: 1.4971 at 20 °C/D; SADTLER REF NUMBER: 532 (IR, PRISM)
Collision Cross Section: 129.98 Å² [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

How is Triethylenetetramine (TETA) Produced?

Triethylenetetramine (TETA) is produced by reacting ethylenediamine (ETA) with ammonia (NH3).
Triethylenetetramine is used for various purposes in multiple industries.

Triethylenetetramine is obtained through the combination of ethylenediamine and ammonia under controlled temperature and pressure conditions.

First, ethylenediamine and ammonia combine, and then this compound is transformed into Triethylenetetramine by removing hydrogen.
The chemical equation for this reaction is as follows:

C2H4(NH2)2 + 4NH3 → (CH2)2(NH)4 + NH3

This process is conducted on an industrial scale and often begins with the hydrochloric acid salt of ethylenediamine.

Alternatively, Triethylenetetramine can also be produced through the reaction between ethylenediamine and aziridine.
However, this method is less common due to higher cost.

Triethylenetetramine appears as a yellowish liquid.
Triethylenetetramine is less dense than water.
Combustible, though may be difficult to ignite.
Triethylenetetramine is corrosive to metals and tissue.
Vapors heavier than air.
Toxic oxides of nitrogen produced during combustion.
Triethylenetetramine is used in detergents and in the synthesis of dyes, pharmaceuticals and other chemicals.

Uses
Epoxy uses
The reactivity and uses of Triethylenetetramine are similar to those for the related polyamines ethylenediamine and diethylenetriamine.
Triethylenetetramine is primarily used as a crosslinker ("hardener") in epoxy curing.
Triethylenetetramine, like other aliphatic amines, react quicker and at lower temperatures than aromatic amines due to less negative steric effects since the linear nature of the molecule provides it the ability to rotate and twist.

Medical uses

The hydrochloride salt of Triethylenetetramine, referred to as trientine hydrochloride, is a chelating agent that is used to bind and remove copper in the body to treat Wilson's disease, particularly in those who are intolerant to penicillamine.
Some recommend trientine as first-line treatment, but experience with penicillamine is more extensive.

Trientine hydrochloride was approved for medical use in the United States in November 1985.

Trientine tetrahydrochloride was approved for medical use in the European Union in September 2017.
Triethylenetetramine is indicated for the treatment of Wilson's disease in adults, adolescents and children five years of age or older who are intolerant to D-penicillamine therapy.

Trientine dihydrochloride was approved for medical use in the European Union in July 2019.
Triethylenetetramine is indicated for the treatment of Wilson's disease in adults, adolescents and children five years of age or older who are intolerant to D-penicillamine therapy.

Production
Triethylenetetramine is prepared by heating ethylenediamine or ethanolamine/ammonia mixtures over an oxide catalyst.
This process gives a variety of amines, especially ethylene amines which are separated by distillation and sublimation.

Coordination chemistry
Triethylenetetramine is a tetradentate ligand in coordination chemistry, where it is referred to as trien.
Octahedral complexes of the type M(trien)L2 can adopt several diastereomeric structures.

Mechanism of action
Wilson's disease is an autosomal recessive genetic disorder that leads to copper accumulation in the tissues.
Triethylenetetramine is characterized by an array of neurologic or psychiatric symptoms as well as liver disease.
One of the treatments for Wilson's disease is the use of copper-chelating agents, such as triethylenetetramine (TETA).
Triethylenetetramine forms a stable complex with copper(II), which is then is readily eliminated through urinary excretion.
Triethylenetetramine also chelates copper in the intestinal tract, reducing intestinal copper absorption by 80%.
Triethylenetetramine and its metabolite, N1-acetyltriethylenetetramine (MAT), are also capable of binding divalent iron, divalent zinc, magnesium, and manganese

Metabolism
The majority of absorbed Triethylenetetramine is extensively metabolized into acetyl-metabolites.
Triethylenetetramine undergoes acetylation mediated by diamine acetyltransferase, also known as spermidine/spermine N1-acetyltranferase, to form two major active metabolites, N1-acetyltriethylenetetramine (MAT) and N1,N10-diacetyltriethylenetetramine (DAT).
The chelating activity of MAT is significantly lower than that of Triethylenetetramine.

Volume of distribution
Triethylenetetramine is widely distributed in tissues, with relatively high concentrations measured in liver, heart, and kidney.
Triethylenetetramine is prone to accumulation in certain tissues.
In healthy adult volunteers receiving oral capsules of Triethylenetetramine, the apparent volume of distribution of steady state was 645 L.

Absorption
Triethylenetetramine is poorly absorbed from the gastrointestinal tract with an oral bioavailability ranging from 6% to 18%.
Triethylenetetramine has the potential to chelate non-copper cations in mineral supplements and other oral drugs, resulting in altered drug absorption; thus, Triethylenetetramine should be administered at least one hour apart from these medications.

The median Tmax ranges from 1.25 to 2 hours.
Mean Cmax (± SD) of triethylenetetramine (TETA) was 2030 ± 981 ng/mL following oral administration of 900 mg TETA and 3430 ± 1480 ng/mL following administration of 1500 mg Triethylenetetramine.
The systemic exposure (AUC) of TETA increased in a dose-proportional manner over the range of 900 mg to 1500 mg TETA.
The mean AUCinf (± SD) was 9750 ± 4910 ngxh/mL at 900 mg and 17200 ± 9470 ngxh/mL at 1500 mg.8

Purification Methods
Dry the amine with sodium, then distil it under a vacuum.
Further purification has been via the nitrate or the chloride salts.
For example, Jonassen and Strickland separated TRIEN from admixture with TREN (38%) by solution in EtOH, cooling to approximately 5o in an ice-bath and adding conc HCl dropwise from a burette, keeping the temperature below 10o, until all of the white crystalline precipitate of TREN.
HCl had formed and was removed.
Further addition of HCl then precipitated thick, creamy white TRIEN.
HCl which was crystallised several times from hot water by adding an excess of cold EtOH.
The crystals were finally washed with Me2CO, then Et2O and dried in a vacuum desiccator.