piperazine

Piperazines were originally named because of their chemical similarity with piperidine, part of the structure of piperine in the black pepper plant (Piper nigrum).{{cite book |first=Alexander |last=Senning |title=Elsevier's Dictionary of Chemoetymology |year=2006 |isbn=978-0-444-52239-9 |location=Amsterdam |publisher=Elsevier}} 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.

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.Ashford's Dictionary of Industrial Chemicals, 3rd edition, 7332{{cite encyclopedia|author=Peter Roose|author2=Karsten Eller |author3=Erhard Henkes |author4=Roland Rossbacher |author5=Hartmut Höke |title=Amines, Aliphatic|encyclopedia=Ullmann's Encyclopedia of Industrial Chemistry|year=2005|publisher=Wiley-VCH|location=Weinheim|doi=10.1002/14356007.a02_001.pub2|isbn=3-527-30673-0 }} The piperazine is separated from the product stream, which, in addition to ethylenediamine, also contains various derivatives containing {{chem2|CH2CH2NH}} 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.{{cn|date=March 2025}}

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.{{cite journal |doi=10.1107/S0108768104003672 |title=Structures of piperazine, piperidine and morpholine |date=2004 |last1=Parkin |first1=Andrew |last2=Oswald |first2=Iain D. H. |last3=Parsons |first3=Simon |journal=Acta Crystallographica Section B Structural Science |volume=60 |issue=2 |pages=219–227 |pmid=15017096 |bibcode=2004AcCrB..60..219P |hdl=20.500.11820/7e7cf6da-259d-4b5e-b2aa-b875aee99d1e |hdl-access=free }}

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.{{cite journal|last1=Rochelle|first1=Gary|last2=Chen|first2=Eric|last3=Freeman|first3=Stephanie|last4=Wagener|first4=David V.|last5=Xu|first5=Qing|last6=Voice|first6=Alexander|title=Aqueous Piperazine as the New Standard for CO₂ Capture Technology|journal=Chemical Engineering Journal|date=15 July 2011|volume=171|issue=3|pages=725–733|doi=10.1016/j.cej.2011.02.011}} Some of the relevant equilibria are:

:{{chem2|HN(CH2CH2)2NH + CO2 <-> H2N+(CH2CH2)2NCO2-}}

:{{chem2|2 HN(CH2CH2)2NH + CO2 <-> HN(CH2CH2)2NCO2- + HN(CH2CH2)2NH2+}}

:{{chem2|H2N+(CH2CH2)2NCO2- + CO2 <-> HO2CN(CH2CH2)2NCO2H}}

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 [CoCl₂(piperazine)]_n, which features tetrahedral cobalt centers linked by bridging piperazine ligands.{{cite journal |doi=10.1016/j.jssc.2006.10.028 |title=Structure Characterization of 1:1 Sdducts of Metal(II) Halides and Piperazine |date=2007 |last1=Yu |first1=Jie-Hui |last2=Hou |first2=Qin |last3=Wang |first3=Tie-Gang |last4=Zhang |first4=Xiao |last5=Xu |first5=Ji-Qing |journal=Journal of Solid State Chemistry |volume=180 |issue=2 |pages=518–522 |bibcode=2007JSSCh.180..518Y }}

Piperazine is easily N-alkylated. Depending on conditions mono- or dialkyl derivatives are obtained.{{cite journal |doi=10.15227/orgsyn.042.0019 |first1=J. Cymerman|last1=Craig|first2= R. J.|last2=Young|title=1-Benzylpiperazine |journal=Organic Syntheses |date=1962 |volume=42 |page=19 }}

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.{{Cite web|last=Imgur|title=imgur.com|url=https://imgur.com/a/gVIqE64|access-date=2021-03-04|website=Imgur|language=en}} 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.{{Cite journal|vauthors = Martin RJ|date=31 July 1997|title=Modes of action of anthelmintic drugs|journal=The Veterinary Journal|volume=154 |issue = 1 |doi=10.1016/S1090-0233(05)80005-X|pages=11–34|pmid=9265850 }}

Piperazine hydrate, piperazine adipate and piperazine citrate (used to treat ascariasis and enterobiasis{{Cite web|url=http://apps.who.int/medicinedocs/en/d/Jh2922e/3.2.4.html|archive-url=https://web.archive.org/web/20100715113324/http://apps.who.int/medicinedocs/en/d/Jh2922e/3.2.4.html|url-status=dead|archive-date=July 15, 2010|title=Helminths: Intestinal nematode infection: Piperazine|date=1995|website=WHO Model Prescribing Information: Drugs Used in Parasitic Diseases - Second Edition|publisher=WHO|access-date=2015-08-29}}) 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).

{{See also|Substituted piperazine}}

Many notable drugs contain a piperazine ring as part of their molecular structure. They may be used as antiparasitic drugs.{{cite book |doi=10.1016/b978-070202858-8.50012-9 |chapter=Antiparasitic drugs |title=Small Animal Clinical Pharmacology |date=2008 |last1=Page |first1=Stephen W. |pages=198–260 |isbn=978-0-7020-2858-8 }} Other examples include:{{Cite web |last=PubChem |title=Piperazine |url=https://pubchem.ncbi.nlm.nih.gov/compound/4837 |access-date=2023-05-03 |website=pubchem.ncbi.nlm.nih.gov |language=en}} 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).

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

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.

• Amine gas treating
• Methyl diethanolamine
• Piperidine

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{{EB1911 poster|Piperazin}}

• {{Cite web|url=http://www.chemicalland21.com/lifescience/UH/PIPERAZINE%20CITRATE.htm|title=PIPERAZINE CITRATE|website=Сhemicalland21.com|access-date=2015-08-29}}

{{Piperazines}}

{{Anthelmintics}}

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Piperazines

Category:Anthelmintics

Category:Diamines