Piperazine
Encyclopedia
Piperazine is an organic compound
that consists of a six-membered ring containing two opposing nitrogen
atoms. Piperazine exists as small alkaline deliquescent crystal
s with a saline
taste.
The piperazines are a broad class of chemical compound
s, many with important pharmacological properties, which contain a core piperazine functional group
.
, 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
.
, but insoluble in diethyl ether
. It is a weak base
with a pKb
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
.
or ethanolamine
. These are the only routes to the chemical used commercially. The piperazine is separated from the product stream, which contains ethylenediamine, diethylenetriamine and other related linear and cyclic chemicals of this type.
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.
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).
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:
Most of these agents can be classified as either phenylpiperazine
s, benzylpiperazine
s, diphenylmethylpiperazine
s (benzhydrylpiperazines), pyridinylpiperazine
s, pyrimidinylpiperazines, or tricyclic
s (with the piperazine ring
attached to the heterocyclic moiety
via a side chain
).
Organic compound
An organic compound is any member of a large class of gaseous, liquid, or solid chemical compounds whose molecules contain carbon. For historical reasons discussed below, a few types of carbon-containing compounds such as carbides, carbonates, simple oxides of carbon, and cyanides, as well as the...
that consists of a six-membered ring containing two opposing nitrogen
Nitrogen
Nitrogen is a chemical element that has the symbol N, atomic number of 7 and atomic mass 14.00674 u. Elemental nitrogen is a colorless, odorless, tasteless, and mostly inert diatomic gas at standard conditions, constituting 78.08% by volume of Earth's atmosphere...
atoms. Piperazine exists as small alkaline deliquescent crystal
Crystal
A crystal or crystalline solid is a solid material whose constituent atoms, molecules, or ions are arranged in an orderly repeating pattern extending in all three spatial dimensions. The scientific study of crystals and crystal formation is known as crystallography...
s with a saline
Salt
In chemistry, salts are ionic compounds that result from the neutralization reaction of an acid and a base. They are composed of cations and anions so that the product is electrically neutral...
taste.
The piperazines are a broad class of chemical compound
Chemical compound
A chemical compound is a pure chemical substance consisting of two or more different chemical elements that can be separated into simpler substances by chemical reactions. Chemical compounds have a unique and defined chemical structure; they consist of a fixed ratio of atoms that are held together...
s, many with important pharmacological properties, which contain a core piperazine functional group
Functional group
In organic chemistry, functional groups are specific groups of atoms within molecules that are responsible for the characteristic chemical reactions of those molecules. The same functional group will undergo the same or similar chemical reaction regardless of the size of the molecule it is a part of...
.
Origin and naming
Piperazines were originally named because of their chemical similarity with piperidinePiperidine
Piperidine is an organic compound with the molecular formula 5NH. This heterocyclic amine consists of a six-membered ring containing five methylene units and one nitrogen atom...
, a constituent of piperine
Piperine
Piperine is the alkaloid responsible for the pungency of black pepper and long pepper, along with chavicine . It has also been used in some forms of traditional medicine and as an insecticide. Piperine forms monoclinic needles, is slightly soluble in water and more so in alcohol, ether or...
in the black pepper
Black pepper
Black pepper is a flowering vine in the family Piperaceae, cultivated for its fruit, which is usually dried and used as a spice and seasoning. The fruit, known as a peppercorn when dried, is approximately in diameter, dark red when fully mature, and, like all drupes, contains a single seed...
plant (Piper nigrum). It is important to note, however, that piperazines are not derived from plants in the Piper
Piper (genus)
Piper, the pepper plants or pepper vines , are an economically and ecologically important genus in the family Piperaceae...
genus
Genus
In biology, a genus is a low-level taxonomic rank used in the biological classification of living and fossil organisms, which is an example of definition by genus and differentia...
.
Chemistry
Piperazine is freely soluble in water and ethylene glycolEthylene glycol
Ethylene glycol is an organic compound widely used as an automotive antifreeze and a precursor to polymers. In its pure form, it is an odorless, colorless, syrupy, sweet-tasting liquid...
, but insoluble in diethyl ether
Diethyl ether
Diethyl ether, also known as ethyl ether, simply ether, or ethoxyethane, is an organic compound in the ether class with the formula . It is a colorless, highly volatile flammable liquid with a characteristic odor...
. It is a weak base
Base (chemistry)
For the term in genetics, see base A base in chemistry is a substance that can accept hydrogen ions or more generally, donate electron pairs. A soluble base is referred to as an alkali if it contains and releases hydroxide ions quantitatively...
with a pKb
PKB
PKB is a three-letter abbreviation that may refer to:* Państwowy Korpus Bezpieczeństwa, a Polish underground police force during World War II* The National Awakening Party of Indonesia, from the abbreviation for its name in Indonesian...
of 4.19; the pH
PH
In chemistry, pH is a measure of the acidity or basicity of an aqueous solution. Pure water is said to be neutral, with a pH close to 7.0 at . Solutions with a pH less than 7 are said to be acidic and solutions with a pH greater than 7 are basic or alkaline...
of a 10% aqueous solution is 10.8-11.8. Piperazine readily absorbs water and carbon dioxide
Carbon dioxide
Carbon dioxide is a naturally occurring chemical compound composed of two oxygen atoms covalently bonded to a single carbon atom...
from the air. Although many piperazine derivatives occur naturally, piperazine itself can be synthesized by reacting alcoholic ammonia
Ammonia
Ammonia is a compound of nitrogen and hydrogen with the formula . It is a colourless gas with a characteristic pungent odour. Ammonia contributes significantly to the nutritional needs of terrestrial organisms by serving as a precursor to food and fertilizers. Ammonia, either directly or...
with 1,2-dichloroethane
1,2-Dichloroethane
The chemical compound 1,2-dichloroethane, commonly known by its old name of ethylene dichloride , is a chlorinated hydrocarbon, mainly used to produce vinyl chloride monomer , the major precursor for PVC production. It is a colourless liquid with a chloroform-like odour...
, by the action of sodium
Sodium
Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...
and ethylene glycol
Ethylene glycol
Ethylene glycol is an organic compound widely used as an automotive antifreeze and a precursor to polymers. In its pure form, it is an odorless, colorless, syrupy, sweet-tasting liquid...
on ethylene diamine
Ethylene diamine
Ethylenediamine is the organic compound with the formula C2H42. This colorless liquid with an ammonia-like odor is a strongly basic amine. The liquid fumes upon contact with humid air...
hydrochloride
Hydrochloride
In chemistry, hydrochlorides are salts resulting, or regarded as resulting, from the reaction of hydrochloric acid with an organic base . This is also known as muriate, derived from hydrochloric acid's other name: muriatic acid....
, or by reduction of pyrazine
Pyrazine
Pyrazine is a heterocyclic aromatic organic compound with the chemical formula C4H4N2.Pyrazine is a symmetrical molecule with point group D2h. Derivatives like phenazine are well known for their antitumor, antibiotic and diuretic activity. Pyrazine is less basic in nature than pyridine, pyridazine...
with sodium in ethanol
Ethanol
Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...
.
Industrial Production
Piperazine is formed as a co-product in the ammoniation of 1,2-dichloroethane1,2-Dichloroethane
The chemical compound 1,2-dichloroethane, commonly known by its old name of ethylene dichloride , is a chlorinated hydrocarbon, mainly used to produce vinyl chloride monomer , the major precursor for PVC production. It is a colourless liquid with a chloroform-like odour...
or ethanolamine
Ethanolamine
Ethanolamine, also called 2-aminoethanol or monoethanolamine , is an organic chemical compound that is both a primary amine and a primary alcohol . Like other amines, monoethanolamine acts as a weak base...
. These are the only routes to the chemical used commercially. 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 anthelminticAnthelmintic
Anthelmintics or antihelminthics are drugs that expel parasitic worms from the body, by either stunning or killing them. They may also be called vermifuges or vermicides .-Pharmaceutical classes:...
in 1953. A large number of piperazine compounds have anthelmintic action. Their mode of action is generally by paralysing
Paralysis
Paralysis is loss of muscle function for one or more muscles. Paralysis can be accompanied by a loss of feeling in the affected area if there is sensory damage as well as motor. A study conducted by the Christopher & Dana Reeve Foundation, suggests that about 1 in 50 people have been diagnosed...
parasites
Parasitism
Parasitism is a type of symbiotic relationship between organisms of different species where one organism, the parasite, benefits at the expense of the other, the host. Traditionally parasite referred to organisms with lifestages that needed more than one host . These are now called macroparasites...
, which allows the host body to easily remove or expel the invading organism. This action is mediated by its agonist
Agonist
An agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...
effects upon the inhibitory GABA (γ-aminobutyric acid) receptor
GABA receptor
The GABA receptors are a class of receptors that respond to the neurotransmitter gamma-aminobutyric acid , the chief inhibitory neurotransmitter in the vertebrate central nervous system...
. Its selectivity for helminths is because vertebrates only use GABA
Gabâ
Gabâ or gabaa, for the people in many parts of the Philippines), is the concept of a non-human and non-divine, imminent retribution. A sort of negative karma, it is generally seen as an evil effect on a person because of their wrongdoings or transgressions...
in the CNS
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
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 BZPBenzylpiperazine
Benzylpiperazine is a recreational drug with euphoric, stimulant properties. The effects produced by BZP are comparable to those produced by amphetamine. Adverse effects have been reported following its use including acute psychosis, renal toxicity, and seizures...
and TFMPP
Trifluoromethylphenylpiperazine
3-Trifluoromethylphenylpiperazine is a recreational drug of the piperazine chemical class. Usually in combination with its analogue benzylpiperazine , it is sold as a legal alternative to the illicit drug MDMA under the name "Legal X".- Pharmacology :TFMPP has affinity for the 5-HT1A , 5-HT1B ,...
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
Methyl diethanolamine
Methyl diethanolamine is a clear, colorless or pale yellow liquid with an ammonia odour. It is miscible with water, alcohol and benzene. Methyl diethanolamine is also known as N-Methyl diethanolamine and more commonly as MDEA. It has the formula CH3N 2. MDEA is a tertiary amine and is widely used...
(MDEA).
Piperazine derivatives as drugs
Piperazine was introduced to medicineMedicine
Medicine is the science and art of healing. It encompasses a variety of health care practices evolved to maintain and restore health by the prevention and treatment of illness....
as a solvent for uric acid
Uric acid
Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates such as ammonium acid urate. Uric acid is created when the body breaks down purine nucleotides. High blood concentrations of uric acid...
. When taken into the body the drug is partly oxidized
Redox
Redox reactions describe all chemical reactions in which atoms have their oxidation state changed....
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
Lysidine (chemical)
Lysidine is an imidazoline derivative. This compound can be an intermediate in the synthesis of metronidazole; it may be prepared by reacting ethylenediamine with acetic acid to give the diamide, followed by treatment with lime. Raney nickel dehydrogenates it to 2-methylimidazole....
and sidonal are compounds having similar action. Many piperazine derivatives are notable successful drugs, including:
Most of these agents can be classified as either phenylpiperazine
Phenylpiperazine
1-Phenylpiperazine is a simple chemical compound featuring a phenyl group bound to a piperazine ring. The suffix '-piprazole' is sometimes used in the names of drugs to indicate they belong to this class....
s, benzylpiperazine
Benzylpiperazine
Benzylpiperazine is a recreational drug with euphoric, stimulant properties. The effects produced by BZP are comparable to those produced by amphetamine. Adverse effects have been reported following its use including acute psychosis, renal toxicity, and seizures...
s, diphenylmethylpiperazine
Diphenylmethylpiperazine
1-piperazine, also known as benzhydrylpiperazine, is a chemical compound and piperazine derivative. It features a piperazine ring with a benzhydryl group bound to one of the nitrogens....
s (benzhydrylpiperazines), pyridinylpiperazine
Pyridinylpiperazine
1-piperazine is a chemical compound and piperazine derivative. Some derivatives of this substance are known to act as potent and selective a2-adrenergic receptor antagonists, such as 1-piperazine....
s, pyrimidinylpiperazines, or tricyclic
Tricyclic
Tricyclics are chemical compounds that contain three interconnected rings of atoms.Many compounds have a tricyclic structure, but in pharmacology, the term has traditionally been reserved to describe heterocyclic drugs...
s (with the piperazine ring
Functional group
In organic chemistry, functional groups are specific groups of atoms within molecules that are responsible for the characteristic chemical reactions of those molecules. The same functional group will undergo the same or similar chemical reaction regardless of the size of the molecule it is a part of...
attached to the heterocyclic moiety
Functional group
In organic chemistry, functional groups are specific groups of atoms within molecules that are responsible for the characteristic chemical reactions of those molecules. The same functional group will undergo the same or similar chemical reaction regardless of the size of the molecule it is a part of...
via a side chain
Side chain
In organic chemistry and biochemistry, a side chain is a chemical group that is attached to a core part of the molecule called "main chain" or backbone. The placeholder R is often used as a generic placeholder for alkyl group side chains in chemical structure diagrams. To indicate other non-carbon...
).