Definition
ChEBI: An azacycloalkane that consists of a six-membered ring containing two nitrogen atoms at opposite positions.
General Description
Needle-like white or colorless crystals. Shipped as a solid or suspended in a liquid medium. Very corrosive to skin, eyes and mucous membranes. Solid turns dark when exposed to light. Flash point 190°F. Used as a corrosion inhibitor and as an insecticide.
Reactivity Profile
PIPERAZINE(110-85-0) neutralizes acids in exothermic reactions to form salts plus water. May be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Absorbs carbon dioxide from the air, which can cause dry crystals to seem to melt. May generate hydrogen, a flammable gas, in combination with strong reducing agents such as hydrides. This compound is sensitive to light; PIPERAZINE(110-85-0) absorbs water and carbon dioxide from air. This compound may be corrosive to aluminum, magnesium and zinc. .
Air & Water Reactions
Flammable. Absorbs water and carbon dioxide from air. Soluble in water.
Health Hazard
TOXIC; inhalation, ingestion or skin contact with material may cause severe injury or death. Contact with molten substance may cause severe burns to skin and eyes. Avoid any skin contact. Effects of contact or inhalation may be delayed. Fire may produce irritating, corrosive and/or toxic gases. Runoff from fire control or dilution water may be corrosive and/or toxic and cause pollution.
Potential Exposure
(Piperazine): Primary irritant (w/o allergic reaction),
Fire Hazard
Combustible material: may burn but does not ignite readily. When heated, vapors may form explosive mixtures with air: indoors, outdoors and sewers explosion hazards. Contact with metals may evolve flammable hydrogen gas. Containers may explode when heated. Runoff may pollute waterways. Substance may be transported in a molten form.
First aid
If this chemical gets into the eyes, remove any contact lenses at once and irrigate immediately for at least 15 minutes, occasionally lifting upper and lower lids. Seek medical attention immediately. If this chemical contacts the skin, remove contaminated clothing and wash immediately with soap and water. Seek medical attention immediately. If this chemical has been inhaled, remove from exposure, begin rescue breathing (using universal precautions, including resuscitation mask) if breathing has stopped and CPR if heart action has stopped. Transfer promptly to a medical facility. When this chemical has been swallowed, get medical attention. If victim is conscious, administer water, or milk. Do not induce vomiting. Medical observation is recommended for 2448 hours after breathing overexposure, as pulmonary edema may be delayed. As first aid for pulmonary edema, a doctor or authorized paramedic may consider administering a drug or other inhalation therapy.
Shipping
UN2579 Piperazine, Hazard class: 8; Labels: 8-Corrosive material.
Incompatibilities
Aqueous solution is a strong base. Violent reaction with strong oxidizers and dicyanofurazan. Incompatible with oxidizers (chlorates, nitrates, peroxides, permanganates, perchlorates, chlorine, bromine, fluorine, etc.); contact may cause fires or explosions. Keep away from alkaline materials, strong bases, strong acids, oxoacids, epoxides, nitrogen compounds, carbon tetrachloride. Attacks aluminum, copper, nickel, magnesium and zinc.
Description
Piperazine is contained in pyrazinobutazone, an equimolecular
sah of piperazine and phenylbutazone.
Among occupational cases, most were reported in the
pharmaceutical industry or laboratory, in nurses and
in veterinarians.
Chemical Properties
Colorless to yellow solid; salty taste.
Chemical Properties
Piperazine is white to cream-colored needles or powder. Characteristic ammonia-like odor. Combustible solids that do not easily ignite.
Uses
keratolytic, antiseborheic
Uses
Piperazine is used as an intermediate in themanufacture of dyes, pharmaceuticals, polymers,surfactants, and rubber accelerators.
Brand name
Pincets (Marion Merrell Dow);
Pinsirup (Marion Merrell Dow);Adelmintex;Adipalis;Adipalit;Adiver;Ancaris thenium;Ancazine;Antelmina;Antepar (b-w);Anterobius;Anthalazine;Anthelmina;Anticucs;Antivermine;Ascalix;Ascarinex;Ascarivet;Asca-trol no.3;Asepar;Askaripar;Averamexan;Bel-zine;Bioxurin;B-piperazine;Brirel;Candizine;Carudol;Ciperazin;Citrazine;Coopane;Dak;Demovermil;Diatesurico;Dicevermin;Digesan;Dilaurazine;Dispermin;Diurazina;Dowzene;Ecosan;Endorid;Entazin;Equizole-a;Escovermin;Esteropipate;Etaphylline (acetyllinate);Gentiazina;Glycopiparsol;Heksapar;Helmacid;Helmezin;Helmicide;Helmifren;Helmipar;Helmirazine (adipate);Helmirazine (citrate);Helmitin;Helmizin;Herb royal round worm treatment;Hexanthelin;Ismiverm;Janes liquid permifu;Jarabe neox;Jetsan supp. (adipate);Justalmin;Kennel-maid;Kihomato;Kontipar;Lamboxil;Lombricida tropico;Lombrifher;Lombrikal;Lombrimade;Mapiprin;Maskito;Noxiurotan;Ogen;Okuside;Optiverm;Oxiril syrup (hydrate);Oxiuran (hydrate);Oxiurasin;Oxiustip elix;Oxivermin;Oxizin;Oxucid;Oxuril;Oxypip;Oxyzin;P.c. (citrate);Padrax;Paravermin;Pariamate;Par-tega;Perin;Piavermit;Pincide;Pipan;Pip-a-ray;Pipenin;Piperacid;Piperamicin;Piperascat;Piperaskat;Piperate;Piperaverm;Piperazinal;Piperazine (adipate);Pipercrean;Piperex;Piperiod;Piperital od;Piperitol;Piper-jodina;Piperol fort;Piperone;Piperoverm;Pipertox;Piperver;Piperzinal;Pipeverm;Pipezol;Pipizan citrate;Pipracid;Piprazid;Piprazyl;Pipricide;Piptelate;Piverma;Polo-verm;Polyquil;Pripsen;Provtovermil;Razinol;Rondelim;Rondoxyl;Santoban;Siropar;Supraverm;Taenifigin;Teniver;Tivazine;Toxocan;Uricida;Uridina;Uroclear (hexamine);Urodan (phosphate);Urosolvina;Uvilon syrup (hydrate);Vanpar (hydrate);Veripar;Vermazine;Vermenter;Vermicompren;Vermidol;Vermifug;Vermilass;Vermipan;Vermiphsarmette;Vermiquimpe;Vermiquimyc;Vermisit;Vermitox;Vermofrik;Verocid;Wairmex;Wurmex;Wurmsirup siegfried
Multifuge;Multifuj;Nea-vermiol;Nemafugan;Nemasin;Nematocton;Nematorazine;Neo-ifusa;.
World Health Organization (WHO)
Piperazine was first used as a treatment for gout earlier this
century and its anthelminthic activity was discovered in 1949. It is also
considerably cheaper than other anthelminthic drugs. In some countries where
ascariasis is not endemic and where piperazine was used predominantly for the
treatment of pinworm it has been withdrawn from use on the grounds that other
more effective and less toxic drugs are now available (see full list). In other such
countries, however, piperazine remains available in over-the-counter preparations.
Clinical dosages occasionally induce transient neurological signs and concern has
been expressed that in some circumstances the drug may generate small amounts
of nitrosamine in the stomach. However, it is widely considered that these trace
doses are unlikely to give rise to a significant carcinogenic potential.
(Reference: (WHODIB) WHO Drug Information Bulletin, 1: 5, , 1983)
Flammability and Explosibility
Highlyflammable
Pharmaceutical Applications
A synthetic chemical, most commonly formulated as the citrate,
but also available as the adipate, edetate calcium and
tartrate salts.
Mechanism of action
Piperazine increases the resting potential
of the somatic musculature of nematodes, especially
in the syncytial region, by increasing the
permeability of the membrane to chloride ions.
This results in flaccid paralysis of the parasites,
which are expelled from the intestine .
Pharmacokinetics
Activity against intestinal worms requires that a substantial
amount remains in the gut. However, after oral administration
a variable amount is rapidly absorbed from the small
intestine and subsequently excreted in the urine. Its half-life
is extremely variable.
Clinical Use
Ascariasis
Pinworm
Clinical Use
Hexahydropyrazine or diethylenediamine (Arthriticine,Dispermin) occurs as colorless, volatile crystals of the hexahydratethat are freely soluble in water. After the discoveryof the anthelmintic properties of a derivative diethylcarbamazine,the activity of piperazine itself was established.Piperazine is still used as an anthelmintic for the treatmentof pinworm (Enterobius [Oxyuris] vermicularis) and roundworm(Ascaris lumbricoides) infestations. It is available invarious salt forms, including the citrate (official in the USP)in syrup and tablet forms. Piperazine blocks the response of the ascaris muscleto acetylcholine, causing flaccid paralysis in the worm,which is dislodged from the intestinal wall and expelled inthe feces.
Synthesis
Piperazine (38.1.12) is a bulk product in organic synthesis. It is made from
ethanolamine by heating it in ammonia at a temperature of 150¨C220??C and a pressure
of 100¨C250atm. It is used as a drug in the form of a salt, and as a rule, in the form of
adipinate.
Veterinary Drugs and Treatments
Piperazine is used for the treatment of ascarids in dogs, cats, horses,
swine and poultry. Piperazine is considered safe to use in animals
with concurrent gastroenteritis and during pregnancy.
Drug interactions
Potentially hazardous interactions with other drugs
Pyrantel: antagonises effect of piperazine.
Carcinogenicity
No increase in lung adenomas
was produced in mice administered 0.69–18.75mg of piperazine/
kg in drinking water for 20–25 weeks and sacrificed
10–13 weeks later. Mice fed the equivalent of
938 mg/kg in the diet for 28 weeks and sacrificed at 40 weeks
failed to show any significant increase in the incidence of
lung adenomas. An increase in lung adenomas was
produced in this bioassay by administration of piperazine
together with sodium nitrate, suggesting the formation of the
active nitroso derivative. Sodium ascorbate inhibited
tumor formation, in theory, by preventing piperazine nitrosation
(304). Coadministration of 250 ppm piperazine and
500 ppm sodium nitrate in drinking water did not produce
tumors in rats. None of these studies were conducted
using currently accepted methods for evaluating carcinogenic
potential but piperazine alone, in these assays, was
noncarcinogenic.
Environmental Fate
This molecule has a simple chemical structure and molecular
weight of 86.14. It has a strong alkaline base soluble in water
(1:18), glycerol, and glycols, but is only sparingly soluble in
alcohol and insoluble in ether. Piperazine is not expected to
hydrolyze in water. The photodegradation half-life is approximately
0.8 h. The piperazine molecule is easily denaturalized
by diverse environmental factors and has a low potential for
bioaccumulation or biomagnification. To improve its stability,
it is usually formulated as different salts such as adipate, citrate,
phosphate, hexahydrate, and sulfate. Most piperazine salts are
white crystalline powders that are readily soluble in water.Exceptions are adipates, which dissolve to only a maximum
concentration of 5% in water, and phosphate, which is
insoluble.
Metabolism
About 25% is metabolised in the liver. Piperazine is
nitrosated to form N -mononitrosopiperazine (MNPz)
in gastric juice, which is then metabolised to N-nitroso-3-
hydroxypyrrolidine (NHPYR).
It is excreted in the urine mainly as metabolites.
Purification Methods
Piperazine crystallises from EtOH or anhydrous *benzene and is dried at 0.01mm. It can be sublimed under vacuum and purified by zone melting. The hydrochloride has m 172-174o (from EtOH), and the dihydrochloride crystallises from aqueous EtOH and has m 318-320o (dec, sublimes at 295-315o). The picrate has m ~200o, and the picrolonate crystallises from dimethylformamide ( m 259-261o). [Beilstein 23 H 4, 23 I 4, 23 II 3, 23 III/IV 15, 23/1 V 30.]
Toxicity evaluation
Piperazine blocks transmission by hyperpolarizing nerve
membranes at the neuromuscular junction, leading to parasite
immobilization by flaccid paralysis and consequent removal
from predilection and death. Piperazine is a selective agonist of
GABA receptors, resulting in the opening of chloride channels
and hyperpolarization of the membrane of the muscle cells of
nematode parasites.
