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Important pharmaceutical intermediates Pharmacology and mechanism of action Indications Side effects Contraindications and precautions Interactions Preparations Acute oral toxicity Data Skin irritation References Flammability and hazardous characteristics Storage characteristics Extinguishing agent Professional standards
Piperazine structure
Chemical Name:
Molecular Formula:
Formula Weight:
MOL File:

Piperazine Properties

Melting point:
109-112 °C(lit.)
Boiling point:
146 °C
1,1 g/cm3
vapor pressure 
0.8 mm Hg ( 20 °C)
refractive index 
Flash point:
65 °C
storage temp. 
Store in dark!
H2O: 0.1 M at 20 °C, clear, colorless
9.83(at 23℃)
Crystalline Flakes
White to slightly yellow
11.0-12.5 (25℃, 0.1M in H2O)
explosive limit
Water Solubility 
150 g/L (20 ºC)
Air Sensitive & Hygroscopic
λ: 260 nm Amax: 0.035
λ: 280 nm Amax: 0.010
JECFA Number
Stable. Hygroscopic. Light sensitive. Flammable. Incompatible with strong oxidizing agents.
CAS DataBase Reference
110-85-0(CAS DataBase Reference)
NIST Chemistry Reference
EPA Substance Registry System
  • Risk and Safety Statements
  • Hazard and Precautionary Statements (GHS)
  • NFPA
Hazard Codes  C,Xn
Risk Statements  34-42/43-52/53-62-52-63
Safety Statements  22-26-36/37/39-45-61
RIDADR  UN 2579 8/PG 3
WGK Germany  1
RTECS  TK7800000
Hazard Note  Harmful/Corrosive
HS Code  2933 59 95
HazardClass  8
PackingGroup  III
Hazardous Substances Data 110-85-0(Hazardous Substances Data)
Toxicity LD50 orally in Rabbit: 2600 mg/kg LD50 dermal Rabbit 8300 mg/kg
Signal word: Danger
Hazard statements:
Code Hazard statements Hazard class Category Signal word Pictogram P-Codes
H314 Causes severe skin burns and eye damage Skin corrosion/irritation Category 1A, B, C Danger P260,P264, P280, P301+P330+ P331,P303+P361+P353, P363, P304+P340,P310, P321, P305+ P351+P338, P405,P501
H317 May cause an allergic skin reaction Sensitisation, Skin Category 1 Warning P261, P272, P280, P302+P352,P333+P313, P321, P363, P501
H334 May cause allergy or asthma symptoms or breathing difficulties if inhaled Sensitisation, respiratory Category 1 Danger P261, P285, P304+P341, P342+P311,P501
H361 Suspected of damaging fertility or the unborn child Reproductive toxicity Category 2 Warning P201, P202, P281, P308+P313, P405,P501
Precautionary statements:
P260 Do not breathe dust/fume/gas/mist/vapours/spray.
P261 Avoid breathing dust/fume/gas/mist/vapours/spray.
P280 Wear protective gloves/protective clothing/eye protection/face protection.
P284 Wear respiratory protection.
P310 Immediately call a POISON CENTER or doctor/physician.
P303+P361+P353 IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P305+P351+P338 IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.
P405 Store locked up.

NFPA 704

Diamond Hazard Value Description
Flammability   2 Must be moderately heated or exposed to relatively high ambient temperature before ignition can occur and multiple finely divided suspended solids that do not require heating before ignition can occur. Flash point between 37.8 and 93.3 °C (100 and 200 °F). (e.g. diesel fuel, sulfur)
Instability   0 Normally stable, even under fire exposure conditions, and is not reactive with water (e.g. helium,N2)

(NFPA, 2010)

Piperazine price More Price(26)

Manufacturer Product number Product description CAS number Packaging Price Updated Buy
Sigma-Aldrich 80621 Piperazine BioUltra, anhydrous, ≥99.0% (T) 110-85-0 25g $65.4 2018-11-13 Buy
Sigma-Aldrich 1541601 Piperazine United States Pharmacopeia (USP) Reference Standard 110-85-0 200mg $348 2018-11-13 Buy
TCI Chemical P0446 Piperazine Anhydrous >98.0%(GC)(T) 110-85-0 25g $15 2018-11-22 Buy
TCI Chemical P0446 Piperazine Anhydrous >98.0%(GC)(T) 110-85-0 500g $40 2018-11-22 Buy
Alfa Aesar A15049 Piperazine, anhydrous, 99% 110-85-0 500g $43.7 2018-11-13 Buy

Piperazine Chemical Properties,Uses,Production

Important pharmaceutical intermediates

Piperazine is an important pharmaceutical intermediate, is mainly used for the production of anthelmintic piperazine phosphate, piperazine citrate and fluphenazine, strong pain, rifampicin, adipic acid piperazine, piperazine guanidine methyl tetracycline, quinoline piperazine phosphate, piperazine thiazole nitrate, enoxacin, hydroxyzine hydrochloride, trifluoperazine, diethylcarbamazine citrate, cinnarizine, flunarizine, decloxizine strong carbamazepine, prednisolone sodium phosphate, dexamethasone sodium phosphate, PPA, norfloxacin, ciprofloxacin, easy to cough piperazine, a piperazine Lee vancomycin, trimethoprim-triazine and other drugs. It is Also used for the production of surfactants products such as wetting agents, emulsifying agents,and dispersing agents ,and the production of plastic additives such as antioxidants, preservatives, stabilizers and rubber additives. It is derived from Dichloroethane by alcohol solution of ammonia.
The structural formula of piperazine
Figure 1 The structural formula of piperazine.

Pharmacology and mechanism of action

Piperazine is a heterocyclic organic base widely used as an anthelminthic. It was originally developed for the treatment of gout. Its first successful use in helminthiasis was reported by Mouriquand et al. in 1951 [1]. Presently the drug is used in the treatment of infections caused by Ascaris lumbricoides and Enterobius vermicularis.
The drug causes flaccid paralysis in susceptible worms and the parasites lose their attachment to the intestinal wall, and are swept away by the normal bowel peristalsis. The biochemical mechanism behind this action is uncertain. Piperazine causes hyperpolarization of the Ascaris muscle rendering it unresponsive to acetylcholine [2].


Treatment of infections due to Ascaris lumbricoides and Enterobius vermicularis. When cost and availability are not a consideration, safer and more effective drugs such as mebendazole or albendazole should be used instead.

Side effects

Side effects commonly encountered with the recommended doses of piperazine are nausea, vomiting, abdominal cramps and diarrhoea which are usually mild and self-limiting. Although absolute incidence is unknown, severe side effects reported in the literature are rare. They can be classified into:
1. Allergic reactions such as urticaria, exantema, hypersensitivity, lacrimation, rhinorrea, productive cough, and bronchospasm[3,4].
2. Neuro-psychological reactions[5-11]:
(a) cerebral type such as vertigo, dizziness, tremor, incoordination, ataxia and hypotonia with EEG changes;
(b) psychic type such as depersonalization, hallucination and paranoic reactions;
(c) miscellaneous such as headache, visual disturbances, somnolence, coma and an increase in the number of petit mal attacks.
Neuro-psychological reactions are rare. Most cases reported concern children with pre disposing factors like neurological symptoms, renal diseases or those who have been treated with high doses of piperazine.
One case of haemolytic anaemia in a patient with G6PD deficiency [12], and one case of toxic hepatitis[13] have also been reported. However, no causal relationships can be established from these cases.
Nitrosation of piperazine to the potential carcinogen N-mononitrosopiperazine in the stomach of patients treated with normal therapeutic doses has been reported[14]. However, carcinogenicity related to the use of piperazine has not been reported despite the use of the drug over many years. In any case, this is unlikely to have any clinical implications with the short treatment period of nematodes.

Contraindications and precautions

Piperazine should not be given to patients with hypersensitivity or with neurological diseases,especially epileptic patients.


In rats and mice, piperazine 1–5 g/kg subcutaneously, potentiates the side effects of chlorpromazine [15]. However, this is unlikely to have any clinical significance. Piperazine is antagonistic to pyrantel, bephenium and levamisole , but no potential clinical interactions have been reported.


Several preparations, apart from the one mentioned below, containing various piperazine salts are available.
• Antepar® (Wellcome). Oral suspension 150 mg piperazine hexahydrate/ml. Tablets 500 mg piperazine hexahydrate.

Acute oral toxicity

rat LD50: 1900 mg/kg; Oral-Mouse LD50: 600 mg/kg

Data Skin irritation

rabbit 500 mg Mild; Eyes-rabbit 0.25 mg/24 hours of severe


1. Mouriquand G, Roman E, Coisnard J (1951). Essai de traitement de l’oxyurose par la piperazine. J Méd Lyon, 32, 189–195.
2. del Castillo J, De Mello WC, Morales T (1964). Mechanism of the paralysing action of piperazine on Ascaris muscle. Br J Pharmacol, 22, 463–477.
3. Macmillan AL (1973). Generalized pustular drug rash. Dermatologia, 146, 285–291.
4. McCullagh SF (1968). Allergenicity of piperazine: a study in environmental aetiology. Br J Ind Med, 25, 319–325.
5. Belloni C, Rizzoni G (1967). Neurotoxic side-effects of piperazine. Lancet, ii, 369.
6. Berger JR, Globus M, Melamed E (1979). Acute transitory cerebellar dysfunction associated with piperazine adipate. Arch Neurol, 36, 180–181.
7. Bomb RS, Bedi HK (1976). Neurotoxic side-effects of piperazine. Trans R Soc Trop Med Hyg, 70, 358.
8. Gupta SR (1976). Piperazine neurotoxicity and psychological reaction. J Ind Med Ass, 66, 33–34.
9. Parsons AC (1971). Piperazine neurotoxicity. ‘Worm wobble’. BMJ, 4, 790–792.
10. Vallat JN, Vallat JM, Texier J, Léger J (1972). Les signes neurologiques d’intoxication par la piperazine. Bordeaux Médicale, 5, 394–400.
11. Nickey LN (1966). Possible precipitation of petit mal seizures with piperazine citrate. J Am Med Ass, 195, 193–194.
12. Buchanan N, Cassel R, Jenkins T (1971). G-6-PD deficiency and piperazine. BMJ, 2, 110.
13. Hamlyn AN, Morris JS, Sarkany I, Sherlock S (1976). Piperazine hepatitis. Gastroenterology, 70, 1144–1147.
14. Bellander T, sterdahl B-G, Hagmar L (1985). Formation of N-mononitrosopiperazine in the stomach and its excretion in the urine after oral intake of piperazine. Toxicol Appl Pharmacol, 80, 193–198.
15. Sturman G (1973). Interaction between piperazine and chlorpromazine. Br J Pharmacol, 50, 153–155.

Flammability and hazardous characteristics

Combustible; decomposition of toxic nitric oxide gas in case of thermal

Storage characteristics

Treasury ventilation low-temperature drying; and stored separately from acid

Extinguishing agent

Water spray, dry powder, carbon dioxide, alcohol-resistant foam

Professional standards

TWA 1 mg/m³; STEL 5 mg/m

Chemical Properties

Piperazine is white to cream-colored needles or powder. Characteristic ammonia-like odor. Combustible solids that do not easily ignite.


Labelled Piperazine


keratolytic, antiseborheic


Piperazine is used as an intermediate in themanufacture of dyes, pharmaceuticals, polymers,surfactants, and rubber accelerators.


ChEBI: An azacycloalkane that consists of a six-membered ring containing two nitrogen atoms at opposite positions.

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)

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.

Air & Water Reactions

Flammable. Absorbs water and carbon dioxide from air. Soluble in water.

Reactivity Profile

1,4-Diazacyclohexane 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. 1,4-Diazacyclohexane is sensitive to light; 1,4-Diazacyclohexane absorbs water and carbon dioxide from air. 1,4-Diazacyclohexane may be corrosive to aluminum, magnesium and zinc. .

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.

Health Hazard

Piperazine is a corrosive substance. The solidand its concentrated aqueous solutions areirritants to the skin and eyes. The irritanteffect in rabbits’ eyes was severe.
The toxic symptoms from ingestion ofpiperazine include nausea, vomiting, excitement,change in motor activity, somnolence,and muscle contraction. The toxicity of thiscompound is low, however. The oral LD50value in rats is 1900 mg/kg. The inhalationtoxicity is very low. The inhalation LC50value in mice is 5400 mg/m3/2 h.

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.

Pharmaceutical Applications

A synthetic chemical, most commonly formulated as the citrate, but also available as the adipate, edetate calcium and tartrate salts.

Contact allergens

Piperazine is contained in pyrazinobutazone, an equimolar salt of piperazine and phenylbutazone. Among occupational cases, most were reported in the pharmaceutical industry or laboratory workers, in nurses, and in veterinarians.


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

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.

Clinical Use


Side effects

Some people develop hypersensitivity, requiring cessation of treatment. Transient, mild gastrointestinal or neurological symptoms may occur.

Safety Profile

Moderately toxic by ingestion, skin contact, intravenous, and subcutaneous routes. Mildly toxic by inhalation. A skin and severe eye irritant. Excessive absorption can cause urticaria, vomiting, diarrhea, blurred vision, and weakness. Combustible when exposed to heat or flame; can react vigorously with oxidizing materials. Explodes on contact with dicyanofurazan. To fight fire, use alcohol foam, mist, dry chemical, water spray. When heated to decomposition it emits highly toxic fumes of NOx.

Potential Exposure

(Piperazine): Primary irritant (w/o allergic reaction),

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.


UN2579 Piperazine, Hazard class: 8; Labels: 8-Corrosive material.

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.]


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.

Piperazine Preparation Products And Raw materials

Raw materials

Preparation Products

Piperazine Suppliers

Global( 320)Suppliers
Supplier Tel Fax Email Country ProdList Advantage
Hefei TNJ Chemical Industry Co.,Ltd.
86-0551-65418684 18949823763
86-0551-65418684 China 1730 55
Capot Chemical Co.,Ltd.
+86 (0)571-855 867 18
+86 (0)571-858 647 95 China 19918 60
Henan Tianfu Chemical Co.,Ltd.
0371-55170693 CHINA 20680 55
Mainchem Co., Ltd.
+86-0592-6210733 CHINA 32457 55
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+8615102730682; +8618874586545
02783214688 CHINA 541 55
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+86-571-86589381/86589382/86589383 CHINA 176 55
Xiamen AmoyChem Co., Ltd
+86 (0)592-605 1114 CHINA 6374 58
Chemwill Asia Co.,Ltd.
86-21-51861608;;; CHINA 24001 58
Hubei Jusheng Technology Co.,Ltd.
86-188-71490254 CHINA 20095 58
Haihang Industry Co.,Ltd
+86 531 8582 1093 CHINA 4669 58

View Lastest Price from Piperazine manufacturers

Image Release date Product Price Min. Order Purity Supply Ability Manufacturer
2018-07-24 Piperazine
US $23.00 / KG 50KG 99% 20T career henan chemical co

Piperazine Spectrum

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