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Piperazine

From Wikipedia - Reading time: 25 min
Piperazine
Names
Preferred IUPAC name
Piperazine[1]
Systematic IUPAC name
1,4-Diazacyclohexane
Other names
Hexahydropyrazine
Piperazidine
Diethylenediamine
1,4-Diazinane
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.003.463 Edit this at Wikidata
KEGG
UNII
  • InChI=1S/C4H10N2/c1-2-6-4-3-5-1/h5-6H,1-4H2 ☒N
    Key: GLUUGHFHXGJENI-UHFFFAOYSA-N ☒N
  • InChI=1S/C4H10N2/c1-2-6-4-3-5-1/h5-6H,1-4H2
  • C1CNCCN1
Properties
C4H10N2
Molar mass 86.138 g·mol−1
Appearance White crystalline solid
Melting point 106 °C (223 °F; 379 K)[2]
Boiling point 146 °C (295 °F; 419 K)[2] Sublimes
Freely soluble[2]
Acidity (pKa) 9.8
Basicity (pKb) 4.19[2]
−56.8·10−6 cm3/mol
Pharmacology
P02CB01 (WHO)
Pharmacokinetics:
60-70%
Hazards
NFPA 704 (fire diamond)
NFPA 704 four-colored diamondHealth 2: Intense or continued but not chronic exposure could cause temporary incapacitation or possible residual injury. E.g. chloroformFlammability 2: Must be moderately heated or exposed to relatively high ambient temperature before ignition can occur. Flash point between 38 and 93 °C (100 and 200 °F). E.g. diesel fuelInstability 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no code
2
2
0
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)

Piperazine (/paɪˈpɛrəziːn/) is an organic compound with the formula (CH2CH2NH)2. In term of its structure, it can be described as cyclohexane with the 1- and 4-CH2 groups replaced by NH.[3] 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, (CH2CH2NH)2·6H2O, which melts at 44 °C and boils at 125–130 °C.[4]

Substituted derivatives of piperazine are a broad class of chemical compounds. Many piperazines have useful pharmacological properties, prominent examples include viagra, ciprofloxacin, and ziprasidone.[5][6]

Origin and naming

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Piperazines were originally named because of their chemical similarity with piperidine, part of the structure of piperine in the black pepper plant (Piper nigrum).[7] 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

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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.[8][9] The piperazine is separated from the product stream, which, in addition to ethylenediamine, also contains various derivatives containing 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.[citation needed]

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.[10]

Reactions

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Its basicity is that of a typical amine. Tthe pH of a 10% aqueous solution of piperazine is 10.8–11.8. The two pKb'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.[11] Some of the relevant equilibria are:

HN(CH2CH2)2NH + CO2 ⇌ H2N+(CH2CH2)2NCO−2
2 HN(CH2CH2)2NH + CO2 ⇌ HN(CH2CH2)2NCO−2 + HN(CH2CH2)2NH+2
H2N+(CH2CH2)2NCO−2 + 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.[12]

Piperazine is easily N-alkylated. Depending on conditions mono- or dialkyl derivatives are obtained.[13]

Uses

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As an anthelmintic

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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.[14] 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.[15]

Piperazine hydrate, piperazine adipate and piperazine citrate (used to treat ascariasis and enterobiasis[16]) 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).[4]

Piperazine derivatives as drugs

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See also: Substituted piperazine

Many notable drugs contain a piperazine ring as part of their molecular structure. They may be used as antiparasitic drugs.[17] Other examples include:[18] 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

[edit]

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

Safety

[edit]

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

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References

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  1. ^ "Front Matter". Nomenclature of Organic Chemistry : IUPAC Recommendations and Preferred Names 2013 (Blue Book). Cambridge: The Royal Society of Chemistry. 2014. p. 142. doi:10.1039/9781849733069-FP001. ISBN 978-0-85404-182-4.
  2. ^ a b c d Merck Index, 11th Edition, 7431
  3. ^ PubChem. "Piperazine". pubchem.ncbi.nlm.nih.gov. Retrieved 2024-03-08.
  4. ^ a b The Merck index, 10th Ed. (1983), p. 1076, Rahway:Merck & Co.
  5. ^ Grygorenko, Oleksandr O.; Radchenko, Dmytro S.; Volochnyuk, Dmitriy M.; Tolmachev, Andrey A.; Komarov, Igor V. (2011). "Bicyclic Conformationally Restricted Diamines". Chemical Reviews. 111 (9): 5506–5568. doi:10.1021/cr100352k. PMID 21711015.
  6. ^ Gee, Paul; Schep, Leo (2013). "1-Benzylpiperazine and other Piperazine-based Derivatives". Novel Psychoactive Substances. pp. 179–209. doi:10.1016/B978-0-12-415816-0.00008-0. ISBN 978-0-12-415816-0.
  7. ^ Senning, Alexander (2006). Elsevier's Dictionary of Chemoetymology. Amsterdam: Elsevier. ISBN 978-0-444-52239-9.
  8. ^ Ashford's Dictionary of Industrial Chemicals, 3rd edition, 7332
  9. ^ Peter Roose; Karsten Eller; Erhard Henkes; Roland Rossbacher; Hartmut Höke (2005). "Amines, Aliphatic". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a02_001.pub2. ISBN 3-527-30673-0.
  10. ^ Parkin, Andrew; Oswald, Iain D. H.; Parsons, Simon (2004). "Structures of piperazine, piperidine and morpholine". Acta Crystallographica Section B Structural Science. 60 (2): 219–227. Bibcode:2004AcCrB..60..219P. doi:10.1107/S0108768104003672. PMID 15017096.
  11. ^ Rochelle, Gary; Chen, Eric; Freeman, Stephanie; Wagener, David V.; Xu, Qing; Voice, Alexander (15 July 2011). "Aqueous Piperazine as the New Standard for CO2 Capture Technology". Chemical Engineering Journal. 171 (3): 725–733. doi:10.1016/j.cej.2011.02.011.
  12. ^ Yu, Jie-Hui; Hou, Qin; Wang, Tie-Gang; Zhang, Xiao; Xu, Ji-Qing (2007). "Structure Characterization of 1:1 Sdducts of Metal(II) Halides and Piperazine". Journal of Solid State Chemistry. 180 (2): 518–522. Bibcode:2007JSSCh.180..518Y. doi:10.1016/j.jssc.2006.10.028.
  13. ^ Craig, J. Cymerman; Young, R. J. (1962). "1-Benzylpiperazine". Organic Syntheses. 42: 19. doi:10.15227/orgsyn.042.0019.
  14. ^ Imgur. "imgur.com". Imgur. Retrieved 2021-03-04.
  15. ^ Martin RJ (31 July 1997). "Modes of action of anthelmintic drugs". The Veterinary Journal. 154 (1): 11–34. doi:10.1016/S1090-0233(05)80005-X. PMID 9265850.
  16. ^ "Helminths: Intestinal nematode infection: Piperazine". WHO Model Prescribing Information: Drugs Used in Parasitic Diseases - Second Edition. WHO. 1995. Archived from the original on July 15, 2010. Retrieved 2015-08-29.
  17. ^ Page, Stephen W. (2008). "Antiparasitic drugs". Small Animal Clinical Pharmacology. pp. 198–260. doi:10.1016/b978-070202858-8.50012-9. ISBN 978-0-7020-2858-8.
  18. ^ PubChem. "Piperazine". pubchem.ncbi.nlm.nih.gov. Retrieved 2023-05-03.
[edit]
Wikisource has the text of the 1911 Encyclopædia Britannica article "Piperazin".
Licensed under CC BY-SA 3.0 | Source: https://en.wikipedia.org/wiki/Piperazine
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