Triethylenetetramine


Triethylenetetramine, also known as trientine when used medically, is an organic compound with the formula 2. The pure free base is a colorless oily liquid, but, like many amines, older samples assume a yellowish color due to impurities resulting from air oxidation. It 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.

Uses

Epoxy uses

The reactivity and uses of TETA are similar to those for the related polyamines ethylenediamine and diethylenetriamine. It is primarily used as a crosslinker in epoxy curing. TETA, 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 TETA, 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. It 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. It 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.
The most common side effects include nausea, especially when starting treatment, skin rash, duodenitis, and severe colitis.

Society and culture

Controversies

In the United States, Valeant Pharmaceuticals International raised the price of its Syprine brand of TETA from $625 to $21,267 for 100 pills over five years. The New York Times said that this "egregious" price increase caused public outrage. Teva Pharmaceuticals developed a generic, which patients and doctors expected to be cheaper, but when it was introduced in February 2018, Teva's price was $18,375 for 100 pills. Aaron Kesselheim, who studies drug pricing at Harvard Medical School, said that drug companies price the product at what they think the market will bear.

Production

TETA 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. An idealized equation follows:

Coordination chemistry

TETA is a tetradentate ligand in coordination chemistry, where it is referred to as trien. Octahedral complexes of the type ML2 can adopt several diastereomeric structures. 1,4,8,11-Tetraazaundecane is a closely related tetraamine ligand.