Piperazine

Piperazine[1]
IUPAC name piperazine
Other names Hexahydropyrazine; Piperazidine; Diethylenediamine
Identifiers
CAS number	110-85-0 Y
PubChem	4837
ChemSpider	13835459 Y
UNII	1RTM4PAL0V
DrugBank	DB00592
KEGG	D00807 N
ChEBI	CHEBI:28568 N
ChEMBL	CHEMBL1412 N
ATC code	P02CB01
Jmol-3D images	Image 1
SMILES C1CNCCN1
InChI InChI=1S/C4H10N2/c1-2-6-4-3-5-1/h5-6H,1-4H2 N Key: GLUUGHFHXGJENI-UHFFFAOYSA-N Y InChI=1S/C4H10N2/c1-2-6-4-3-5-1/h5-6H,1-4H2
Properties
Molecular formula	C4H10N2
Molar mass	86.14 g mol−1
Appearance	White crystalline solid
Melting point	106 °C, 379 K, 223 °F ([2])
Boiling point	146 °C, 419 K, 295 °F ([2])
Solubility in water	Freely soluble[2]
Acidity (pKa)	4.19[2]
Pharmacology
Protein binding	60-70%
Hazards
NFPA 704	2 2 0
N (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Piperazine is an organic compound that consists of a six-membered ring containing two opposing nitrogen atoms. Piperazine exists as small alkaline deliquescent crystals with a saline taste.

The piperazines are a broad class of chemical compounds, many with important pharmacological properties, which contain a core piperazine functional group.

Origin and naming

Piperazines were originally named because of their chemical similarity with piperidine, a constituent of piperine in the black pepper plant (Piper nigrum). It is important to note, however, that piperazines are not derived from plants in the Piper genus.

Chemistry

Piperazine is freely soluble in water and ethylene glycol, but insoluble in diethyl ether. It is a weak base with a pK_b of 4.19; the pH of a 10% aqueous solution is 10.8-11.8. Piperazine readily absorbs water and carbon dioxide from the air. Although many piperazine derivatives occur naturally, piperazine itself can be synthesized by reacting alcoholic ammonia with 1,2-dichloroethane, by the action of sodium and ethylene glycol on ethylene diamine hydrochloride, or by reduction of pyrazine with sodium in ethanol.

Industrial Production

Piperazine is formed as a co-product in the ammoniation of 1,2-dichloroethane or ethanolamine. These are the only routes to the chemical used commercially.^[3] The piperazine is separated from the product stream, which contains ethylenediamine, diethylenetriamine and other related linear and cyclic chemicals of this type.

As an anthelmintic

Piperazine was first introduced as an anthelmintic in 1953. A large number of piperazine compounds have anthelmintic action. Their mode of action is generally by paralysing parasites, which allows the host body to easily remove or expel the invading organism. This action is mediated by its agonist effects upon the inhibitory GABA (γ-aminobutyric acid) receptor. Its selectivity for helminths is because vertebrates only use GABA in the CNS and the helminths' GABA receptor is a different isoform to the vertebrate's one. Piperazine hydrate and piperazine citrate are the main anthelminthic piperazines. These drugs are often referred to simply as "piperazine" which may cause confusion between the specific anthelmintic drugs and the entire class of piperazine-containing compounds.

Other uses

Piperazines are also used in the manufacture of plastics, resins, pesticides, brake fluid and other industrial materials. Piperazines, especially BZP and TFMPP have become an extremely common adulterant in the club and rave scene, often being passed off as MDMA, although they do not share many similarities in their effects.

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

Piperazine derivatives as drugs

Piperazine was introduced to medicine as a solvent for uric acid. When taken into the body the drug is partly oxidized and partly eliminated unchanged. Outside the body, piperazine has a remarkable power to dissolve uric acid and producing a soluble urate, but in clinical experience it has not proved equally successful. Lycetol, lysidine and sidonal are compounds having similar action. Many piperazine derivatives are notable successful drugs, including:

Antianginals

• Ranolazine
• Trimetazidine

Antidepressants

• Alnespirone
• Amoxapine
• Befuraline
• Binospirone
• Buspirone
• Flesinoxan
• Gepirone
• Ipsapirone
• Nefazodone
• Piberaline
• Tandospirone
• Trazodone
• Vilazodone
• Zalospirone

Antihistamines

• Buclizine
• Meclozine
• Cinnarizine
• Cyclizine
• Hydroxyzine
• Cetirizine
• Levocetirizine
• Niaprazine

Antipsychotics

• Typical
  • Fluphenazine
  • Perphenazine
  • Trifluoperazine
  • Prochlorperazine
  • Thiothixene
  • Flupentixol
  • Zuclopenthixol
• Atypical
  • Amperozide
  • Aripiprazole
  • Lurasidone
  • Clozapine
  • Olanzapine
  • Perospirone
  • Ziprasidone

Recreational Drugs

• 4-Bromo-2,5-dimethoxy-1-benzylpiperazine (2C-B-BZP)
• 1-Benzylpiperazine (BZP)
• 2,3-Dichlorophenylpiperazine (DCPP)
• 1,4-Dibenzylpiperazine (DBZP)
• 4-Methyl-1-benzylpiperazine (MBZP)
• 3-Chlorophenylpiperazine (mCPP)
• 3,4-Methylenedioxy-1-benzylpiperazine (MDBZP)
• 4-Methoxyphenylpiperazine (MeOPP)
• 4-Chlorophenylpiperazine (pCPP)
• 4-Fluorophenylpiperazine (pFPP)
• 3-Trifluoromethylphenylpiperazine (TFMPP)

Urologicals

• Sildenafil
• Vardenafil

Others

• 6-Nitroquipazine
• Antrafenine
• Fipexide
• Imatinib
• Piperazine (itself)
• Quipazine

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).

See also

• Pyridine
• Piperidine

References

1. ^ Merck Index, 11th Edition, 7431.
2. ^ ^{a b c d} Merck Index, 11th Edition, 7431
3. ^ Ashford’s Dictionary of Industrial Chemicals, 3rd edition, 7332

•  Chisholm, Hugh, ed (1911). "Piperazin". Encyclopædia Britannica (11th ed.). Cambridge University Press. 

External links

• Piperazine citrate at Chemicalland21