Piperazine

HCID 4837CAS 110-85-0

Basic information

Standard SMILES
C1CNCCN1
InChIKey
GLUUGHFHXGJENI-UHFFFAOYSA-N
Molecular formula
C4H10N2
Average molar mass
86.14 g/mol
Monoisotopic mass
86.08439832

Overview

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.

Names & identifiers

Preferred name
Piperazine
IUPAC
piperazine
English name
Piperazine
Molecular formula
C4H10N2
Molecular weight
86.14

Names & synonyms

piperazine110-85-0Diethylenediamine1,4-DiazacyclohexaneHexahydropyrazinePiperazinAntirenPiperazidineDiethyleneimineDispermineLumbricalPipersol
Show more names
Piperzine AnhydrousPiperazine HexahydrtaeAnhydrous Piperazine (PIP)Upixon
Eraverm1,4-PiperazineWurmirazinUvilonPiperazine, anhydrousWorm-A-Ton1,4-DiethylenediaminePyrazine hexahydride

Database identifiers

CAS
110-85-0
PubChem CID
4837
DTXSID
DTXSID1021164
ChEMBL
CHEMBL1412
ChEBI
CHEBI:28568
UNII
1RTM4PAL0V
EC Number
203-808-3
Nikkaji
J1.981J

Properties

Computed structural properties

XLogP
-1.5
Topological polar surface area
24.1 Ų
Hydrogen bond donors
2
Hydrogen bond acceptors
2
Rotatable bonds
0
Heavy atoms
6

Experimental & physicochemical properties

Chemical Classes · 2 items

Nitrogen Compounds -> Piperazines

Corrosives

PFASPFAS -> Other/unspecified
Drugs · 2 items

DEA NFLIS-Drug Category -> Piperazines (Hallucinogen)

Pharmaceuticals -> Listed in ZINC15

pHpH = 10.8-11.8 (10% aqueous solution)
SpringerMaterials Properties15N nuclear magnetic resonance spectrum
LogP · 4 items

log Kow = -1.50

-0.8

-1.17

-1.17

Physicochemical properties

Melting point
109 · 109-112 °C (lit.)
Boiling point
145 · 145-146 °C (lit.)
Density
1 · 1,1 g/cm3
bulk density
400 kg/m3 · 400kg/m3
vapor pressure
0.8 mm · 0.8 mm Hg ( 20 °C)
refractive index
1.446 · 1.4460

Safety & regulation

GHS classification

GHS Classification · 6 items

Danger

H314: Causes severe skin burns and eye damage [Danger Skin corrosion/irritation]

P203, P233, P260, P261, P264, P271, P272, P280, P284, P301+P330+P331, P302+P352, P302+P361+P354, P304+P340, P305+P354+P338, P316, P318, P321, P333+P317, P342+P316, P362+P364, P363, P403, P405, and P501 (click each P-code to see the statement)

Danger

H314: Causes severe skin burns and eye damage [Danger Skin corrosion/irritation]

P203, P233, P260, P261, P264, P271, P272, P280, P284, P301+P330+P331, P302+P352, P302+P361+P354, P304+P340, P305+P354+P338, P316, P318, P321, P333+P317, P342+P316, P362+P364, P363, P403, P405, and P501 (click each P-code to see the statement)

Hazard information

Regulatory Information · 6 items

Chemical: Piperazine

Hazard Traits - Respiratory Toxicity

Commission Regulation (EC) No 1565/2000 (Repealed by Com. Implementing Reg. (EU) No 872/2012)

Piperazine is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of Piperazine are required to report information about their production and use of this chemical to the EPA under the Toxic Substances Control Act (TSCA). (40 eCFR Part 711)

Status: Active Update: 22-02-2023 https://echa.europa.eu/registration-dossier/-/registered-dossier/14941

Piperazine: Does not have an individual approval but may be used under an appropriate group standard

Other Safety InformationIMAP assessments - Piperazine: Human health tier II assessment
DOT LabelCorrosive
Fire Hazards · 3 items

Excerpt from ERG Guide 153 [Substances - Toxic and/or Corrosive (Combustible)]:

· Combustible material: may burn but does not ignite readily.

Combustible. Gives off irritating or toxic fumes (or gases) in a fire. Above 65 °C explosive vapour/air mixtures may be formed.

Fire PotentialCombustible when exposed to heat or flame.
Health Hazards · 2 items

Excerpt from ERG Guide 153 [Substances - Toxic and/or Corrosive (Combustible)]:

· TOXIC and/or CORROSIVE; inhalation, ingestion or skin contact with material may cause severe injury or death.

Safety & protection

Fire Fighting · 2 items

Excerpt from ERG Guide 153 [Substances - Toxic and/or Corrosive (Combustible)]:

Use water spray, powder, alcohol-resistant foam, carbon dioxide.

First Aid Measures · 4 items

Fresh air, rest. Half-upright position. Artificial respiration may be needed. Refer for medical attention.

Remove contaminated clothes. Rinse skin with plenty of water or shower for at least 15 minutes. Refer for medical attention .

First rinse with plenty of water for several minutes (remove contact lenses if easily possible), then refer for medical attention.

Rinse mouth. Do NOT induce vomiting. Refer for medical attention .

Accidental Release Measures · 2 items

· CALL 911. Then call emergency response telephone number on shipping paper. If shipping paper not available or no answer, refer to appropriate telephone number listed on the inside back cover.

· ELIMINATE all ignition sources (no smoking, flares, sparks or flames) from immediate area.

First Aid · 2 items

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

General First Aid:

Safe StorageSeparated from strong acids, strong oxidants, acid anhydrides, metals and food and feedstuffs. Dry. Well closed.
Exposure Control and Personal Protection· Wear positive pressure self-contained breathing apparatus (SCBA).

Toxicology

Interactions · 4 items

In mice, doses of about 625 mg piperazine base/kg bw (6,250 mg/kg feed( was administered for 28 weeks together with 0.1% nitrite in the drinking water. After an additional period of 12 weeks on a basal diet without piperazine and nitrite, a 10 fold increase in numbers of lung adenomas vs control numbers was observed. MIce receiving piperazine alone during the same time period showed afterwards no increase in tumor incidence.

In a different study an increased frequency of lung adenomas in mice was seen when oral doses corresponding to 1,250 mg piperazine/kg bw/day plus 5 mg sodium nitrite/kg bw/day or 138 mg piperazine/kg bw/day plus 200 mg sodium nitrite/kg bw/day were given. Doses of 1,250 mg piperazine.kg bw.day plus 1 mg sodium nitrite/kg bw/day did not result in any increased tumor frequency. In rats receiving 30 mg piperazing/kg bw/day plus 70 mg (0.05%) nitrite daily for 75 weeks there was no increase in tumor incidence.

High doses of piperazine may enhance the effects of chlorpromazine and increase the risk of seizures; concurrent use is not recommended.

Pyrantel may antagonize the anthelmintic effect of piperazine; concurrent use is not recommended.

Environmental Fate · 3 items

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 3.6(SRC), determined from a log Kow of -1.50(2) and a regression-derived equation(3), indicates that piperazine is expected to have very high mobility in soil(SRC). Measured pKa values of 9.73 (first nitrogen) and 5.33 (second nitrogen)(4) indicate that piperazine will exist primarily in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5). Volatilization of piperazine from moist soil surfaces is not expected to be an important fate process(SRC) since cations do not volatilize. Piperazine is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 0.16 mm Hg(6). Piperazine may biodegrade in soil based on greater than 51% biodegradation measured after 28 days in a artificial river water total organic carbon (TOC) die-away test; however, only 1.4% degradation occurred after 14 days during a MITI screening test(7,8).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 3.6(SRC), determined from a log Kow of -1.50(2) and a regression-derived equation(3), indicates that piperazine is not expected to adsorb to suspended solids and sediment(SRC). However, measured pKa values of 9.73 (first nitrogen) and 5.33 (second nitrogen)(4) indicate piperazine will exist almost entirely in the cation form at pH values of 5 to 9 and cations adsorb to suspended solids and sediment more strongly than their neutral counterparts(5). Volatilization of piperazine from water surfaces is not expected to be an important fate process since cations do not volatilize. According to a classification scheme(6), a BCF range of less than 0.3-0.9(7) suggests the potential for bioconcentration in aquatic organisms is low(SRC). Piperazine may biodegrade in water based on greater than 51% biodegradation measured after 28 days in a artificial river water total organic carbon (TOC) die-away test; however, only 1.4% degradation occurred after 14 days during a MITI screening test(7,8).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), piperazine, which has a vapor pressure of 0.16 mm Hg at 20 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase piperazine is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 2.3 hours(SRC), calculated from its rate constant of 1.7X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Piperazine does not contain chromophores that absorb at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight(4).

Adverse EffectsNeurotoxin - Other CNS neurotoxin
Exposure RoutesThe substance can be absorbed into the body by inhalation and by ingestion.
Milk ConcentrationsEXPERIMENTAL: Piperazine is thought to be distributed into breast milk but no definitive information is available.
Signs and Symptoms · 4 items

Burning sensation. Cough. Sore throat. Shortness of breath. Laboured breathing. Wheezing.

Skin burns. Pain. Blisters.

Redness. Pain. Severe burns.

Burning sensation. Abdominal pain. Nausea. Vomiting. Headache. Weakness. Convulsions. Shock or collapse.

Regulatory information

FDA Requirements · 5 items

Piperazine is an indirect food additive for use as a component of adhesives.

Oral dosage form new animal drug. Piperazine citrate capsules. ...Specifications. Piperazine citrate capsules contain piperazine citrate equivalent to 140 milligrams of piperazine base in each capsule. ... Conditions of use. (1) It is used in dogs and cats for the removal of large roundworms (Toxocara canis and Toxascaris leonina). /Piperazine citrate/

Oral dosage form new animal drug. Piperazine phosphate capsules. ... Specifications. Each capsule contains 120, 300, or 600 milligrams of piperazine phosphate monohydrate. ... Indications for use: (i) Dogs. It is used for the removal of large roundworms (ascarids) Toxocara canis and Toxascaris leonina. (ii) Cats. It is used for the removal of large roundworms (ascarids) Toxocara mystax and Toxacaris leonina. /Piperazine phosphate/

Oral dosage form new animal drug. Piperazine suspension. ... Specifications. Each milliliter of suspension contains piperazine monohydrochloride equivalent to 33.5 milligrams (mg) piperazine base. ... Conditions of use in dogs-(1) Indications for use. For the removal of roundworms (Toxocara canisand Toxascaris leonina).

For more FDA Requirements (Complete) data for PIPERAZINE (7 total), please visit the HSDB record page.

Atmospheric Standards · 1 item

This action promulgates standards of performance for equipment leaks of Volatile Organic Compounds (VOC) in the Synthetic Organic Chemical Manufacturing Industry (SOCMI). The intended effect of these standards is to require all newly constructed, modified, and reconstructed SOCMI process units to use the best demonstrated system of continuous emission reduction for equipment leaks of VOC, considering costs, non air quality health and environmental impact and energy requirements. Piperazine is produced, as an intermediate or a final product, by process units covered under this subpart.

Safety data

F
3-8-23
PPE
Eyeshields, Faceshields, Gloves, type P3 (EN 143) respirator cartridges
wgk
1
tsca
TSCA listed
rtecs
TK7800000
ridadr
UN 2579

Chemistry & industry

Pharmacology

ATC Code · 2 items

P - Antiparasitic products, insecticides and repellents

QP - Antiparasitic products, insecticides and repellents

Protein Binding60-70%
Pharmacodynamics · 1 item

Piperazine is an anthelminthic especially useful in the treatment of partial intestinal obstruction caused by Ascaris worms, which is a condition primarily seen in children. Piperazine hydrate and piperazine citrate are the main anthelminthic piperazines.

Mechanism of Action · 6 items

Piperazine is a GABA receptor agonist. Piperzine binds directly and selectively to muscle membrane GABA receptors, presumably causing hyperpolarization of nerve endings, resulting in flaccid paralysis of the worm. While the worm is paralyzed, it is dislodged from the intestinal lumen and expelled live from the body by normal intestinal peristalsis.

Piperazine blocks the response of the /target species/ worm muscle (best studied in Ascaris), causing flaccid paralysis of the worm. While the worm is paralyzed, it is dislodged from the intestinal lumen and expelled live from the body by normal intestinal peristalsis.

The predominant effect of piperazine on /the target species/ Ascaris is to cause a flaccid paralysis that results in expulsion of the worm by peristalsis. ... Piperazine blocks the response of Ascaris muscle to acetylcholine, apparently by altering the permeability of the cell membrane to ions that are responsible for the maintenance of the resting potential. The drug causes hyperpolarization and suppression of spontaneous spike potentials with accompanying paralysis.

Piperazine citrate causes reversible muscle paralysis in intestinal nematodes, presumably by causing hyperpolarization of nerve endings /in this target species/. /Piperazine citrate/

Piperazine and its salts, as a gamma-aminobutyric acid (GABA)-like substance, induce a reversible flaccid paralysis in the /target/ nematode parasites. This is provoked by a hyperpolarization of the cell membrane followed by suppression of spontaneous spike potentials. THe paralyzed nematodes are expelled from the gut lumen by normal peristaltic actions.

In mammals, motorcortical GABAa inhibition is important for initiation of smooth flexion and/or extension movements of the extremities affecting motor and postural control. When injected into the hand motor cortical area of three infant macaque monkeys, the GABA agonist muscimol disrupted forelimb movement showing a posture of dropped wrist and fingers as if the radial nerve were paralysed. Interestingly, the three investigated animals exhibited large inter-individual differences in sensitivity to the action of the same dose of muscimol, being low in one, moderate in the second and substantial in the third. Injection into the medial segment of globus pallidus elicited choreiform movements and injections into substantia nigra pars reticulata provoked severe axial posture anomalies with rotational behaviour as well as contralateral hypotonia. Although the symptoms induced by piperazine in sensitive species exhibits some of these features, it is possible that its effects in mammals also involve other modes of action as well, in as much as a nicotinic action on rat sympathetic ganglia in vitro was reported in one series of experiments.

Biological Half-Life · 2 items

Following oral administration in humans, piperazine has shown to be absorbed rapidly and to be excreted predominantly and quickly in the urine. During the first 24 hours after administration nearly 40% of the dose was excreted. The shape of the curve for the elimination of piperazine in urine indicates at least two phases in excretion. For the fastest and dominating phase the half life is in the order of a couple of hours.

Plasma half-life is highly variable.

Metabolism/Metabolites · 5 items

About 25% is metabolized in the liver. Piperazine is nitrosated to form N -mononitrosopiperazine (MNPz) in gastric juice, which is then metabolized to N-nitroso-3-hydroxypyrrolidine (NHPYR).

In three studies, orally administered piperazine to humans was nitrosated to N-mononitrosopiperazine to an extent of respectively 0.1, 1 and 5%. ... It seems probable that 1,4-dinitrosopiperazine, not N-mononitrosopiperazine, is the carcinogenic nitrosamine of piperazine. 1,4-Dinitrosopiperazine could not be detected in the analysis of human gastric juice, blood or urine after ingestion of piperazine.

/In 4 hens/ the major component in excreta was unchanged piperazine (approximately 60% at 24 hours and approximately 50% at 7 days after administration. /In 2 pigs/ the major component in both urine and feces was unchanged piperazine (in urine respectively 82% and 61% at 24 hours and 168 hours after administration), although some unidentified metabolites were present in both excreta. /Piperazine dihydrochloride/

Approximately 25% is metabolized in the liver. Piperazine is nitrosated to from N-mononitrosopiperazine (MNPz) in gastric juice and further metabolized to N-nitroso-3-hydroxypyrrolidine (NHPYR).

Piperazine is partly metabolized in an unknown manner in man, since only 15% of 2 g doses are excreted unchanged.

Uses & manufacturing

Uses · 6 items

Piperazine salts are used as anthelmintic drugs; Also used to make corrosion inhibitors, insecticides, curing agents for polychloroprene, and antihistamines; [HSDB] Used to make fibers, drugs, and insecticides; Also used in veterinary medicine to eradicate pinworms; [ACGIH]

MEDICATION

MEDICATION (VET)

Piperazine is used as a scruber in gas-washer formulations; as a hardener for glue prepolymers; as an intermediate in the preparation of hydroxyethyl piperazine, N,N'-dimethyl piperazine, and N-methyl piperazine; and as a raw material to prepare intermediates used for antihistamine production. Piperazine salts are human and veterinary medicinal drugs used as anthelmintics.

In mfg of ... corrosion inhibitors, surface-active agents

For more Uses (Complete) data for PIPERAZINE (6 total), please visit the HSDB record page.

U.S. Production · 6 items

2023: 10,000,000 - <50,000,000 lb

This chemical is listed as a High Production Volume (HPV) (65FR81686). Chemicals listed as HPV were produced in or imported into the U.S. in >1 million pounds in 1990 and/or 1994. The HPV list is based on the 1990 Inventory Update Rule. (IUR) (40 CFR part 710 subpart B; 51FR21438).

Production volumes for non-confidential chemicals reported under the Inventory Update Rule. [Table#2810]

(1972) 1.6X10+9 GRAMS

(1975) 1.49X10+9 GRAMS

For more U.S. Production (Complete) data for PIPERAZINE (7 total), please visit the HSDB record page.

Consumption Patterns · 2 items

ESSENTIALLY ALL PIPERAZINE PRODUCED IS CONVERTED TO PIPERAZINE SALTS (1975)

ESSENTIALLY 100% FOR ANTHELMINTIC USE (1976) /PIPERAZINE HYDROCHLORIDE/

Industry UsesIntermediate
Methods of Manufacturing · 5 items

Condensation & de-amination of diethylenetriamine; condensation of diethanolamine in the presence of ammonia; condensation & dehydration of monethanolamine

The ethanol amine based process: Piperazine is synthesized by reaction of ethanolamine with ammonia under high pressure over a catalyst in the presence of hydrogen to produce a mixture of ethylene amines, e.g. piperazine, as well as water as by-product. The ethyleneamines are separated via distillation. Sometimes this process is integrated with the ethanolamine process. The ethanol amine is synthesized by reaction of ethylene oxide with a large excess of ammonia in a liquid phase to produce a mixture of mono-, di-, and triethanolamines. This reaction takes place in a high pressure reactor over an ion exchange catalyst. The excess of ammonia is recovered by distillation and recycled to the reactor.

The ethylene dichloride based process. Ethylene dichloride is reacted with an excess of ammonia under high pressure and moderate temperature. The resultant ethylene amine hydrochloride solution is neutralized with caustic soda to form piperazine and other ethylene amines, which are subsequently isolated by distillation. Sodium chloride is formed as a by-product.

/It is/ prepared by action of alcoholic ammonia on ethylene chloride. By reduction of pyrazine with sodium in alcohol.

For more Methods of Manufacturing (Complete) data for PIPERAZINE (7 total), please visit the HSDB record page.

Formulations/Preparations · 5 items

U.S.- Not commercially available. Canada-2 grams per packet (Rx) (Entacyl (sodium <19.2 mg)). /Piperazine adipate granules for oral solution/

U.S.- Not commercially available. Canada- 600 mg per 5 mL (Rx) (Entacyl (sodium <0.8 mg)).

U.S.- 250 mg (hexahydrate) (275.75 mg piperazine citrate anhydrous) (Rx) (GENERIC). Canada- Not commercially available. /Piperazine citrate Tablets USP/

Piperazine salts are available as tablets & wafers, each containing 500 mg, & as syrups & suspensions containing 100 mg/mL, calculated as hexahydrate. ... Piperazine citrate, USP, and piperazine phosphate, NF, are official preparations. Trade names include Antepar (citrate & phosphate), Multifuge citrate and Pipizan citrate.

For more Formulations/Preparations (Complete) data for PIPERAZINE (10 total), please visit the HSDB record page.

Applications · 6 items

DescriptionPiperazine 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.

DescriptionPiperazine (Item No. 24019) is an analytical reference standard categorized as a piperazine. This product is intended for research and forensic applications.

UsesLabelled Piperazine

Useskeratolytic, antiseborheic

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

General DescriptionNeedle-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.

Additional notes

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

Related reactions

3,819 records

Linked notes

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