Piperazine

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Structural formula
Structural formula of piperazine
General
Surname Piperazine
other names
  • 1,4-diethylenediamine
  • 1,4-diazinane ( IUPAC )
Molecular formula C 4 H 10 N 2
Brief description

flaky, colorless crystals, amine-like odor

External identifiers / databases
CAS number
  • 110-85-0
  • 142-63-2 (hexahydrate)
  • 207605-49-0 (di hydrochloride hydrate)
PubChem 4837
DrugBank DB00592
Wikidata Q409292
Drug information
ATC code

P02 CB01

properties
Molar mass 86,14 g · mol -1
Physical state

firmly

density

1.1 g cm −3 (20 ° C)

Melting point

111-113 ° C

boiling point

146 ° C

solubility

easily in water (150 g l −1 at 20 ° C)

Refractive index

1.446 (113 ° C)

safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS hazard labeling from  Regulation (EC) No. 1272/2008 (CLP) , expanded if necessary
08 - Dangerous to health 05 - Corrosive

danger

H and P phrases H: 314-317-334-361fd
P: 261-280-305 + 351 + 338-310
Toxicological data
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . Refractive index: Na-D line , 20 ° C

The piperazine is an organic, heterocyclic compound. Pure piperazine is a white, highly hygroscopic powder, the taste of which is described as salty and bitter.

history

Piperazine got its name because of its similarity to piperidine , a component of the alkaloid piperine found in black pepper .

Piperazine was the first drug that Schering AG brought onto the market in 1890 . Originally intended as a rejuvenator , it was later used first to treat gout and then as an anthelmintic . Today piperazine is a starting material for the synthesis of medicinal substances .

Extraction and presentation

Piperazine can be prepared by reaction of ammonia with 1,2-dichloroethane in ethanol or by reduction of pyrazine with sodium are presented in ethanol. It is a by-product of the industrial production of ethylene diamine . The quantities formed are so large that specific production is not necessary to meet commercial demand.

properties

Piperazine is well soluble in water, somewhat less soluble in alcohol, and not soluble in ether . It is highly hygroscopic and, in the presence of water, forms whitish crystals with a content of 44.34% anhydrous piperazine, piperazine hexahydrate ( CAS number : 142-63-2). The hexahydrate, like other salts (adipate, chloride, citrate), is more stable than anhydrous piperazine. In addition, piperazine is a strong base with a pK B of 4.19. A 10% aqueous solution of piperazine shows a pH of 10.8-11.8.

use

Piperazine and its derivatives in medicine

Piperazine for gout

Historic advertisement for piperazine

The historical use of piperazine in the treatment of gout based on the observation that in vitro , the uric acid can dissolve. However, the effectiveness in vivo , i.e. in the human body, was significantly lower . Piperazine is well absorbed, but is also quickly excreted. It is excreted in the urine.

Piperazine as an anthelmintic

Piperazine was somewhat more successful as an anti-wormer agent. It was used both in veterinary medicine and in human medicine for worm infestation, for example by roundworms and oxyurs , but has now been replaced by more tolerable anthelmintics or those with a broader spectrum of activity. Due to the salty-bitter taste and the chemical instability, no pure piperazine ( piperazine base ) was used, but one of the much more stable salts, usually piperazine citrate or adipate. Since it was known that potentially mutagenic and carcinogenic N -nitrosopiperazines can form in the acidic environment of the stomach , piperazine salts have now been completely replaced by other preparations. The effectiveness of piperazine against worms was first based on the inhibiting effect of acetylcholine . The blockage of this neurotransmitter would lead to a paralysis of the parasites, so that the transmission of excitation between nerves and muscles would be disrupted. This coincided with the observation that the parasites, although paralyzed but still alive, are excreted in the feces.

It is now known that piperazine has a GABA- agonistic effect. This neurotransmitter occurs in vertebrates only in the CNS , and the GABA receptor of worms (helminths) differs somewhat from that of vertebrates, which explains the selective effect of piperazine. Exact dosing of piperazine or piperazine salts is necessary, however, since an overdose crosses the blood-brain barrier in mammals .

Piperazine derivatives as drugs

A piperazine partial structure can be found in a number of drugs:

Other uses

Piperazine is u. a. used as a raw material for the manufacture of plastics. Polyester urethanes are obtained by reacting ethylene carbonate with piperazine and then reacting with dicarboxylic acid dichlorides.

A number of piperazine derivatives are also used as psychoactive drugs, e.g. B. benzylpiperazine (BZP), trifluoromethylphenylpiperazine (TFMPP) or meta-chlorophenylpiperazine (mCPP).

Piperazine is also used as an additive in alkali carbonate-based acid gas scrubbing processes, such as the Benfield process (Hot potassium carbonate process).

safety instructions

The symptoms of an overdose of piperazine are mainly shown by the occurrence of neurotoxic side effects ( tremor , ataxia , convulsions , paresis ) and gastrointestinal complaints ( vomiting , diarrhea ). Typical of a poisoning by piperazine is the delayed appearance of the symptoms after about 24 hours.

Web links

  • Entry on piperazine at Vetpharm, accessed on August 5, 2012.

Individual evidence

  1. ↑ a b c d e f g Entry on piperazine in the GESTIS substance database of the IFA , accessed on July 23, 2016(JavaScript required) .
  2. ↑ David R. Lide (Ed.): CRC Handbook of Chemistry and Physics . 90th edition. (Internet version: 2010), CRC Press / Taylor and Francis, Boca Raton, FL, Physical Constants of Organic Compounds, pp. 3-436.
  3. ↑ Entry on Piperazine in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), accessed on February 1, 2016. Manufacturers or distributors can expand the harmonized classification and labeling .
  4. ^ R. Cavier: Chemotherapy of intestinal nematodes. In: Chemotherapy of helminthiasis , Pergamon Press, Oxford (UK), 1, 1973, pp. 215-436.
  5. ↑ a b C.H. Courtney et al .: Antinematodal Drugs. In: Veterinary Pharmacology and Therapeutics Iowa State University Press, Ames (USA), 1995, pp. 885-932, ISBN 0-8138-1741-2 .
  6. ↑ J. Del Castillo et al .: Inhibitory action of gamma-aminobutyric acid (GABA) of Ascaris muscle. In: Experientia 20, 1964, pp. 141-143, PMID 5853680 .
  7. ^ J. Del Castillo et al .: Action of piperazine on the neuromuscular system of Ascaris lumbricoides. , In: Nature , 200, 1963, pp. 706-707, PMID 14109979 .
  8. ^ BR Manger: Anthelmintics. In: Veterinary Applied Pharmacology & Therapeutics , Baillière Tindall, London (UK) 1991, pp. 513-548, ISBN 0-7020-1366-8 .
  9. ^ ML Aubry: Aspects of the pharmacology of a new anthelmintic: Pyrantel. In: Br J Pharmacol , 38, 1970, pp. 332-344, PMID 5417856 .
  10. ^ RJ Martin: Electrophysiological effects of piperazine and diethylcarbamazine on Ascaris suum somatic muscle. In: Br J Pharmacol , 77, 1982, pp. 255-265, PMID 7139188 .
  11. ↑ P. Behr, A. Maun, K. Deutgen, A. Tunnat, G. Oeljeklaus: Kinetic study on promoted potassium carbonate solutions for CO2 capture from flue gas . In: Energy Procedia . tape 4 , 2011, p. 85-92 , doi : 10.1016 / j.egypro.2011.01.027 .
  12. ↑ D. Kömpf, B. Neundörfer: Neurotoxic side effects of piperazine in adulthood - epileptic twilight state with myoclonus. In: European Archives of Psychiatry and Clinical Neuroscience , 213 (3), 1974, pp. 223-233, doi : 10.1007 / BF02401381 .
  13. ↑ P. Schuch et al .: Side effects of wormer cures with piperazine preparations. In: European Journal of Pediatrics , 87 (6), 1963, pp. 531-546, doi : 10.1007 / BF00447192 .