Piperazine

Piperazine () is an organic compound with the formula . In term of its structure, it can be described as cyclohexane with the 1- and 4-CH₂ groups replaced by NH. Piperazine exists as deliquescent solid with a saline taste. Piperazine is freely soluble in water and ethylene glycol, but poorly soluble in diethyl ether. Piperazine is commonly available industrially is as the hexahydrate, , which melts at 44 °C and boils at 125–130 °C.''The Merck index, 10th Ed.'' (1983), p. 1076, Rahway:Merck & Co.

Substituted derivatives of piperazine are a broad class of chemical compounds. Many piperazines have useful pharmacological properties, prominent examples include viagra, ciprofloxacin, and ziprasidone.

Origin and naming

Piperazines were originally named because of their chemical similarity with piperidine, part of the structure of piperine in the black pepper plant (''Piper nigrum''). The -az- infix added to "piperazine" refers to the extra nitrogen atom, compared to piperidine. It is important to note, however, that piperazines are ''not'' derived from plants in the '' Piper'' genus.

Synthesis and structure

Piperazine is formed by the ammoniation of 1,2-dichloroethane or ethanolamine. This reaction is mainly used for production of ethylene diamine, but piperazine is a side product. The piperazine is separated from the product stream, which, in addition to ethylenediamine, also contains various derivatives containing subunits, e.g. diethylenetriamine, aminoethylpiperazine, and other related linear and cyclic chemicals of this type.

Piperazine can also be synthesized by reduction of pyrazine with sodium in ethanol.

As confirmed by X-ray crystallography, piperidine is a centrosymmetric molecule. The ring adopts a chair conformation and the two N-H groups are equatorial.

Reactions

Its basicity is that of a typical amine. The pH of a 10% aqueous solution of piperazine is 10.8–11.8. The two pK_b's are 5.35 and 9.73 at 25 °C.

Piperazine readily absorbs water and carbon dioxide from the air. Carbon dioxide produce a series of carbamates. Some of the relevant equilibria are:
:
:
:

As a basic amine, piperazine forms a variety of coordination complexes, usually binding to metals as a unidentate ligand (bidentate binding would require the boat conformation). One example is the polymer oCl₂(piperazine)sub>n, which features tetrahedral cobalt centers linked by bridging piperazine ligands.

Piperazine is easily N-alkylated. Depending on conditions mono- or dialkyl derivatives are obtained.

Uses

As an anthelmintic

Piperazine was marketed by Bayer as an anthelmintic in the early 20th century, and was featured in print ads alongside other popular Bayer products at the time, including heroin. In fact, a large number of piperazine compounds have an anthelmintic action. Their mode of action is generally by paralysing parasites, which allows the host body to easily expel the invasive organism. The neuromuscular effects are thought to be caused by blocking acetylcholine at the myoneural junction. This action is mediated by its agonist effects upon the inhibitory GABA (γ-aminobutyric acid) receptor. Its selectivity for helminths is because vertebrates use GABA only in the CNS, and the GABA receptor of helminths is of a different isoform from that of vertebrates.

''Piperazine hydrate'', ''piperazine adipate'' and ''piperazine citrate'' (used to treat ascariasis and enterobiasis) are the most common anthelmintic piperazine compounds. These drugs are often referred to simply as "piperazine" which may cause confusion between the specific anthelmintic drugs, the entire class of piperazine-containing compounds, and the compound itself.

Two common salts in the form of which piperazine is usually prepared for pharmaceutical or veterinary purposes are the citrate, 3C₄H₁₀N₂·2C₆H₈O₇ (i.e. containing 3 molecules of piperazine to 2 molecules of citric acid), and the adipate, C₄H₁₀N₂·C₆H₁₀O₄ (containing 1 molecule each of piperazine and adipic acid).

Piperazine derivatives as drugs

Many notable drugs contain a piperazine ring as part of their molecular structure. They may be used as antiparasitic drugs. Other examples include: Diethylcarbamazine, a derivative of piperazine, is used to treat some types of filariasis.

Most of these agents can be classified as either phenylpiperazines, benzylpiperazines, diphenylmethylpiperazines (benzhydrylpiperazines), pyridinylpiperazines, pyrimidinylpiperazines, or tricyclics (with the piperazine ring attached to the heterocyclic moiety via a side chain).

Other uses

Piperazine is also a fluid used for CO₂ and H₂S scrubbing in association with methyl diethanolamine (MDEA).

Safety

Piperazines, such as BZP and TFMPP were common adulterants in the club and rave scene, often being passed off as MDMA, although they do not share many similarities in their effects.

See also

* Amine gas treating
* Methyl diethanolamine
* Piperidine

References

External links

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Piperazines
Anthelmintics
Diamines