# Piperazine

**Piperazine** is an organic compound, C₄H₁₀N₂, consisting of a saturated six-membered ring with two nitrogen atoms at opposite (1 and 4) positions; it is best known as an anthelmintic drug that paralyzes intestinal roundworms, and it is also a widely used building block in pharmaceuticals and a promoter in industrial carbon dioxide capture solvents.<sup>[1](https://pubchem.ncbi.nlm.nih.gov/compound/Piperazine)</sup><sup> • </sup><sup>[2](https://www.ebi.ac.uk/chebi/CHEBI%3A28568)</sup>

| Key fact | Detail |
|---|---|
| Structure | Saturated six-membered ring, two nitrogen atoms at the 1 and 4 positions; formula C₄H₁₀N₂, molecular weight 86.14 g/mol, CAS 110-85-0<sup>[1](https://pubchem.ncbi.nlm.nih.gov/compound/Piperazine)</sup> |
| Basicity | Two protonatable secondary amines with pKa values of 9.73 (first nitrogen) and 5.33 (second nitrogen), so it exists mainly as a cation at environmental pH<sup>[1](https://pubchem.ncbi.nlm.nih.gov/compound/Piperazine)</sup> |
| Physical properties | Melting point 106 °C, boiling point 146 °C, density 1.1 g/cm³, solubility 15 g/100 mL water at 20 °C<sup>[3](https://www.inchem.org/documents/icsc/icsc/eics1032.htm)</sup> |
| Anthelmintic use | Introduced as an anthelmintic in 1953; acts as a GABA receptor agonist on nematode muscle, producing flaccid paralysis<sup>[1](https://pubchem.ncbi.nlm.nih.gov/compound/Piperazine)</sup><sup> • </sup><sup>[4](https://www.sciencedirect.com/science/article/pii/S109002330580005X)</sup>  |
| Industrial role | Most commonly used promoter for CO₂ absorption in amine solvents such as MDEA/PZ blends for syngas and natural gas treatment<sup>[5](https://www.bcinsight.crugroup.com/wp-content/uploads/sites/7/2025/02/NS_337.pdf)</sup> |
| Pharmaceutical presence | Over 60 FDA-approved drugs contain a piperazine ring, including ciprofloxacin and cetirizine<sup>[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC5818626/)</sup><sup> • </sup><sup>[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC12816771/)</sup>  |
| Handling hazard | Corrosive to eyes, skin, and respiratory tract; occupational exposure limit 0.03 ppm as TWA<sup>[3](https://www.inchem.org/documents/icsc/icsc/eics1032.htm)</sup> |

## Chemistry and physical properties

Piperazine is a cyclic diamine: both ring nitrogens are secondary amines, which makes the molecule two basic centers that can be substituted or protonated independently.<sup>[8](https://www.aladdinsci.com/us_es/faqs/piperazine-selection-guide-using-a-to-make-salt-forms-and-linking-strategies-en.html)</sup> The measured pKa values of 9.73 and 5.33 mean that at pH values between 5 and 9 the compound exists almost entirely in cationic form, which affects its adsorption to soil, its lack of volatilization from water, and its formulation as salts.<sup>[1](https://pubchem.ncbi.nlm.nih.gov/compound/Piperazine)</sup> Pharmaceutical preparations commonly use salts such as the citrate, phosphate, adipate, and dihydrochloride.<sup>[1](https://pubchem.ncbi.nlm.nih.gov/compound/Piperazine)</sup>

In the solid state, anhydrous piperazine crystallizes in the space group P2₁/n with the molecule in the chair conformation, and N–H···N hydrogen bonds of 2.319 Å link molecules into sheets.<sup>[9](https://www.pure.ed.ac.uk/ws/files/9098400/Structures_of_piperazine_piperidine_and_morpholine.pdf)</sup> A hexahydrate also exists, in which hydrogen-bonded water layers connect to the ring nitrogens.<sup>[10](https://colab.ws/articles/10.1063%2F1.1669751)</sup>

## Manufacture

The main industrial route reacts ethanolamine with ammonia under high pressure over a hydrogenation catalyst in the presence of hydrogen, producing a mixture of ethylene amines that includes piperazine.<sup>[1](https://pubchem.ncbi.nlm.nih.gov/compound/Piperazine)</sup> Patent processes from the early 1960s describe heating monoethanolamine, diethanolamine, or triethanolamine with a molar excess of ammonia at roughly 150 to 400 °C and 30 to 400 atmospheres over nickel, copper, or cobalt catalysts; reported piperazine yields in the examples ranged from about 17.9% to 37% of theory depending on the starting amine and catalyst.<sup>[11](https://patents.google.com/patent/US3037023A/en)</sup> Other routes condense ethylenediamine with glycols or cyclize diethylenetriamine and aminoethylethanolamine.<sup>[12](https://www.researchgate.net/publication/358196552_Methods_for_the_catalytic_synthesis_of_piperazine)</sup>

## Anthelmintic action

Piperazine was first used as an anthelmintic in the 1950s and remains the active constituent of over-the-counter remedies for threadworm infection in children.<sup>[13](https://www.ncbi.nlm.nih.gov/books/NBK116072/)</sup> Its target is the GABA-gated chloride channel on nematode body wall muscle. These inhibitory channels mediate the relaxation phase of the worm's sinusoidal movement; by acting as a GABA agonist, piperazine opens the chloride channels, increasing chloride conductance and hyperpolarizing the muscle membrane, which produces a flaccid, reversible paralysis.<sup>[4](https://www.sciencedirect.com/science/article/pii/S109002330580005X)</sup><sup> • </sup><sup>[14](https://pmc.ncbi.nlm.nih.gov/articles/PMC3898135/)</sup><sup> • </sup><sup>[15](https://eprints.soton.ac.uk/466425/1/1133073.pdf)</sup>  The paralyzed worms cannot hold their position in the intestine against peristalsis and are expelled in the feces.<sup>[16](https://www.sciencedirect.com/topics/neuroscience/piperazine)</sup>

Electrophysiological work on *Ascaris suum* somatic muscle measured GABA and piperazine reversal potentials with voltage clamp, confirming that the drug acts on the same inhibitory conductance as GABA.<sup>[17](https://pubmed.ncbi.nlm.nih.gov/7139188/)</sup> Studies in *Caenorhabditis elegans* compared wild-type and *unc-49* mutants, which encode GABA<sub>A</sub>-like receptor subunits at the body wall neuromuscular junction, suggesting piperazine may interact with other putative GABA-gated chloride channels such as LGC-37, LGC-38, and GAB-1.<sup>[13](https://www.ncbi.nlm.nih.gov/books/NBK116072/)</sup>

The drug is effective against larger gastrointestinal nematodes but has a limited spectrum, and GABA agonists as a class were not developed beyond piperazine.<sup>[18](https://pmc.ncbi.nlm.nih.gov/articles/PMC3732103/)</sup> Nematode resistance to piperazine, along with all other available anthelmintic classes, has been documented.<sup>[19](https://www.nature.com/articles/s41598-023-50305-y)</sup> A related compound, diethylcarbamazine, is a piperazine derivative but is not a GABA agonist; it acts on arachidonic acid metabolism and the innate immune response, and one of its mammalian metabolites is piperazine itself.<sup>[18](https://pmc.ncbi.nlm.nih.gov/articles/PMC3732103/)</sup>

## Piperazine as a drug scaffold

The piperazine ring is one of the most frequently used N-heterocycles in pharmaceutical small molecules, ranked behind piperidine and pyridine, and more than 60 FDA-approved drugs contain it.<sup>[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC5818626/)</sup><sup> • </sup><sup>[20](https://pmc.ncbi.nlm.nih.gov/articles/PMC8698587/)</sup>  The ring contributes a large polar surface area, conformational rigidity, and hydrogen-bond donors and acceptors, which can improve target affinity, water solubility, and oral bioavailability.<sup>[20](https://pmc.ncbi.nlm.nih.gov/articles/PMC8698587/)</sup>

Examples span several therapeutic areas. The fluoroquinolone antibiotic ciprofloxacin carries a piperazine ring to increase bacterial enzyme binding and membrane permeability, and the antihistamine cetirizine uses it to tune receptor affinity and pharmacokinetics.<sup>[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC12816771/)</sup> Piperazine-containing compounds also act on G-protein-coupled receptors such as dopamine D₂ and serotonin 5-HT₁A/₂A in antipsychotics and antidepressants, and on calcium and sodium channels in drugs for epilepsy and migraine.<sup>[21](https://chemistry-europe.onlinelibrary.wiley.com/doi/full/10.1002/open.202500366)</sup>

## Carbon dioxide capture

Piperazine has a second, unrelated industrial life as an amine solvent for CO₂ absorption. It is the most commonly used promoter for CO₂ removal from syngas and from natural gas in LNG production, added in small concentrations to activate less reactive amines such as MDEA.<sup>[5](https://www.bcinsight.crugroup.com/wp-content/uploads/sites/7/2025/02/NS_337.pdf)</sup> Because its solubility in water is low, working concentrations run between 0.5 and 2.5 M, and increasing the piperazine fraction raises both solvent capacity and absorption kinetics.<sup>[22](https://pmc.ncbi.nlm.nih.gov/articles/PMC3947793/)</sup> Compared with the benchmark solvent monoethanolamine, piperazine absorbs CO₂ roughly twice as fast, which explains its use as a kinetic promoter in blended formulations.<sup>[23](https://doi.org/10.1016/j.rineng.2025.108910)</sup> Degradation under process conditions, thermal and oxidative, depends on piperazine concentration, CO₂ loading, temperature, oxygen partial pressure, and metal ions such as Cu²⁺, and nitrosamine formation and decay are part of the degradation chemistry.<sup>[24](https://www.sciencedirect.com/science/article/pii/S1750583614002941)</sup>

## Safety and environmental behavior

Anhydrous piperazine is a hygroscopic, corrosive solid that burns skin and eyes and can cause lung edema after inhalation; repeated contact may sensitize the skin and cause asthma.<sup>[3](https://www.inchem.org/documents/icsc/icsc/eics1032.htm)</sup> The American Conference of Governmental Industrial Hygienists threshold limit value is 0.03 ppm as an eight-hour time-weighted average, with a notation for skin and respiratory sensitization.<sup>[3](https://www.inchem.org/documents/icsc/icsc/eics1032.htm)</sup> In the environment, the compound is highly mobile in soil (estimated Koc 3.6), shows low bioconcentration potential in fish, and degrades slowly: only 1.4% of theoretical BOD was reached in two weeks in a standard MITI activated-sludge test, though more than 51% degraded after 28 days in some river-water microcosms.<sup>[1](https://pubchem.ncbi.nlm.nih.gov/compound/Piperazine)</sup>

## References

1. [Piperazine, CID 4837, PubChem](https://pubchem.ncbi.nlm.nih.gov/compound/Piperazine)
2. [piperazine (CHEBI:28568), ChEBI](https://www.ebi.ac.uk/chebi/CHEBI%3A28568)
3. [ICSC 1032: Piperazine (anhydrous), ILO/WHO International Chemical Safety Cards](https://www.inchem.org/documents/icsc/icsc/eics1032.htm)
4. [Martin, R.J. (1997). Modes of action of anthelmintic drugs. The Veterinary Journal 154(1): 11-34](https://www.sciencedirect.com/science/article/pii/S109002330580005X)
5. [CO₂ Removal from Syngas, Nitrogen+Syngas (BCInsight)](https://www.bcinsight.crugroup.com/wp-content/uploads/sites/7/2025/02/NS_337.pdf)
6. [Expedient syntheses of N-heterocycles via intermolecular amphoteric diamination of allenes, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC5818626/)
7. [Piperazine Derivatives: A Privileged Scaffold in Modern Synthesis and Medicinal Chemistry, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC12816771/)
8. [Piperazine Selection Guide, Aladdin Scientific](https://www.aladdinsci.com/us_es/faqs/piperazine-selection-guide-using-a-to-make-salt-forms-and-linking-strategies-en.html)
9. [Parkin, A. et al. (2004). Structures of piperazine, piperidine and morpholine. Acta Crystallographica B60: 219-227](https://www.pure.ed.ac.uk/ws/files/9098400/Structures_of_piperazine_piperidine_and_morpholine.pdf)
10. [Structure of Piperazine Hexahydrate, CoLab](https://colab.ws/articles/10.1063%2F1.1669751)
11. [US3037023A: Process for preparation of piperazine, Google Patents](https://patents.google.com/patent/US3037023A/en)
12. [Methods for the catalytic synthesis of piperazine, ResearchGate](https://www.researchgate.net/publication/358196552_Methods_for_the_catalytic_synthesis_of_piperazine)
13. [Anthelmintic drugs and nematicides: studies in Caenorhabditis elegans, WormBook, NCBI Bookshelf](https://www.ncbi.nlm.nih.gov/books/NBK116072/)
14. [Ion channels and receptor as targets for the control of parasitic nematodes, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC3898135/)
15. [Anthelmintics that act on the GABA receptor, University of Southampton thesis](https://eprints.soton.ac.uk/466425/1/1133073.pdf)
16. [Piperazine: an overview, ScienceDirect Topics](https://www.sciencedirect.com/topics/neuroscience/piperazine)
17. [Electrophysiological effects of piperazine and diethylcarbamazine on Ascaris suum somatic muscle, PubMed](https://pubmed.ncbi.nlm.nih.gov/7139188/)
18. [Control of nematode parasites with agents acting on neuro-musculature systems, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC3732103/)
19. [Anthelmintic efficacy evaluation and mechanism of N-methylbenzo[d]oxazol-2-amine, Scientific Reports](https://www.nature.com/articles/s41598-023-50305-y)
20. [Piperazine based antimicrobial polymers: a review, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC8698587/)
21. [Piperazine Derivatives: A Privileged Scaffold, ChemistryOpen (Wiley)](https://chemistry-europe.onlinelibrary.wiley.com/doi/full/10.1002/open.202500366)
22. [Carbon Dioxide Separation from Flue Gases: A Technological Review, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC3947793/)
23. [Advances in amine-based absorption solvent engineering, Results in Engineering](https://doi.org/10.1016/j.rineng.2025.108910)
24. [Degradation study of piperazine, its blends and structural analogs for CO₂ capture: A review, International Journal of Greenhouse Gas Control](https://www.sciencedirect.com/science/article/pii/S1750583614002941)

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*Topic: Encyclopedia › Physical world and mathematics › Chemistry › Organic substances › Amines and nitrogen functional groups › Aliphatic amines and polyamines › Diamines and polyamines › Ethylenediamine and higher ethyleneamines*

*Initially written Sep 17, 2026 · Reviewed: Sep 30, 2026; Oct 15, 2026 · Edited: Oct 15, 2026 · Last review: Oct 15, 2026*

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