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2-Imidazoline (
A variety of routes exist for the synthesis of imidazolines, with the most common methods involving the condensation of 1,2-diamines (e.g.
File:Clonidine.png, Clonidine
File:Example_of_imidazoline_as_catalyst.png, Biimidazoline ligands and a complex.
File:Grubbs_catalyst_Gen2.svg, Second generation
Preferred IUPAC name
In chemical nomenclature, a preferred IUPAC name (PIN) is a unique name, assigned to a chemical substance and preferred among all possible names generated by IUPAC nomenclature. The "preferred IUPAC nomenclature" provides a set of rules for choo ...
: 4,5-dihydro-1''H''-imidazole) is one of three isomers of the nitrogen
Nitrogen is a chemical element; it has Symbol (chemistry), symbol N and atomic number 7. Nitrogen is a Nonmetal (chemistry), nonmetal and the lightest member of pnictogen, group 15 of the periodic table, often called the Pnictogen, pnictogens. ...
-containing heterocycle
A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different elements as members of its ring(s). Heterocyclic organic chemistry is the branch of organic chemistry dealing with the synthesis, proper ...
imidazoline
Imidazoline is a heterocycle formally derived from imidazole by the reduction of one of the two double bonds. Three isomers are known, 2-imidazolines, 3-imidazolines, and 4-imidazolines. The 2- and 3-imidazolines contain an imine center, whereas t ...
, with the formula C3H6N2. The 2-imidazolines are the most common imidazolines commercially, as the ring exists in some natural product
A natural product is a natural compound or substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life. Natural products can also be prepared by chemical s ...
s and some pharmaceuticals
Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy ( pharmacotherapy) is an important part of the ...
. They also have been examined in the context of organic synthesis
Organic synthesis is a branch of chemical synthesis concerned with the construction of organic compounds. Organic compounds are molecules consisting of combinations of covalently-linked hydrogen, carbon, oxygen, and nitrogen atoms. Within the gen ...
, coordination chemistry
A coordination complex is a chemical compound consisting of a central atom or ion, which is usually metallic and is called the ''coordination centre'', and a surrounding array of chemical bond, bound molecules or ions, that are in turn known as ' ...
, and homogeneous catalysis
In chemistry, homogeneous catalysis is catalysis where the catalyst is in same phase as reactants, principally by a soluble catalyst in a solution. In contrast, heterogeneous catalysis describes processes where the catalysts and substrate are in d ...
.
Synthesis
A variety of routes exist for the synthesis of imidazolines, with the most common methods involving the condensation of 1,2-diamines (e.g. ethylenediamine
Ethylenediamine (abbreviated as en when a ligand) is the organic compound with the formula C2H4(NH2)2. This colorless liquid with an ammonia-like odor is a basic amine. It is a widely used building block in chemical synthesis, with approximately ...
) with nitriles
In organic chemistry, a nitrile is any organic compound that has a functional group. The name of the compound is composed of a base, which includes the carbon of the , suffixed with "nitrile", so for example is called "propionitrile" (or pro ...
or esters
In chemistry, an ester is a chemical compound, compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds c ...
. The nitrile based route is essentially a cyclic Pinner reaction
The Pinner reaction refers to the acid catalysed reaction of a nitrile with an alcohol to form an imino ester salt (alkyl imidate salt); this is sometimes referred to as a Pinner salt.
The reaction is named after Adolf Pinner, who first described ...
; it requires high temperatures and acid catalysis and is effective for both alkyl and aryl nitriles.
As natural products
Imidazoline has been found in various natural products. Natural molecules topsentin D and spongotine B were discovered in several marine sponges. These metabolites have received considerable attention because of their potent properties such asantitumor
Cancer treatments are a wide range of treatments available for the many different types of cancer, with each cancer type needing its own specific treatment. Treatments can include surgery, chemotherapy, radiation therapy, hormonal therapy, targe ...
, antiviral
Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Antiviral drugs are a class of antimicrobials ...
, and anti-inflammatory
Anti-inflammatory is the property of a substance or treatment that reduces inflammation, fever or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs reduce pain by inhibiting mechan ...
activities.
Biological role
Many imidazolines are biologically active. Most bio-active derivatives bear a substituent (aryl
In organic chemistry, an aryl is any functional group or substituent derived from an aromatic ring, usually an aromatic hydrocarbon, such as phenyl and naphthyl. "Aryl" is used for the sake of abbreviation or generalization, and "Ar" is used ...
or alkyl
In organic chemistry, an alkyl group is an alkane missing one hydrogen.
The term ''alkyl'' is intentionally unspecific to include many possible substitutions.
An acyclic alkyl has the general formula of . A cycloalkyl group is derived from a cy ...
group) on the carbon between the nitrogen centers. Some generic names include oxymetazoline
Oxymetazoline, sold under the brand name Afrin among others, is a topical decongestant and vasoconstrictor medication. It is available over-the-counter as a nasal spray to treat nasal congestion and nosebleeds, as eye drops to treat eye rednes ...
, xylometazoline
Xylometazoline, also spelled xylomethazoline, is a medication used to reduce symptoms of nasal congestion, allergic rhinitis, and sinusitis. It is used directly in the nose as a spray or drops.
Side effects include trouble sleeping, irritati ...
, tetrahydrozoline
Tetryzoline (International Nonproprietary Name, INN), also known as tetrahydrozoline, is a drug used in some over-the-counter eye drops and nasal sprays. Tetryzoline was patented in 1954, and came into medical use in 1959.
Side effects
Tetryzol ...
, and naphazoline
Naphazoline is a medicine used as a decongestant, and a vasoconstrictor added to eye drops to relieve red eye. It has a rapid action in reducing swelling when applied to mucous membranes. It is a sympathomimetic agent with marked alpha adrener ...
.
Applications
Pharmaceutical
2-imidazolines have been investigated as antihyperglycemic, anti-inflammatory, antihypertensive, antihypercholesterolemic, and antidepressant reagents. The imidazoline-containing drug clonidine is used alone or in combination with other medications to treat high blood pressure. It is also used in the treatment of dysmenorrhea, hypertensive crisis, Tourette's syndrome and attention deficit hyperactivity disorder (ADHD).Grubbs' catalyst Grubbs catalysts are a series of transition metal carbene complexes used as catalysts for olefin metathesis. They are named after Robert H. Grubbs, the chemist who supervised their synthesis. Several generations of the catalyst have also been develo ...
File:Spongotine B.png, Spongotine B
As p53 activators
''Cis''-imidazolines act as small-molecule antagonists of MDM2. These compounds bind MDM2/X in the p53-binding pocket and activate the p53 pathway in cancer cells, leading to cell cycle arrest, apoptosis, and growth inhibition of human tumor xenografts in nude mice. The most active compounds are nutlin-3a and rg-7112, but some other analogs also activate p53.Surfactants
Surfactant
Surfactants are chemical compounds that decrease the surface tension or interfacial tension between two liquids, a liquid and a gas, or a liquid and a solid. The word ''surfactant'' is a Blend word, blend of "surface-active agent",
coined in ...
s based around 2-imidazoline, such as sodium lauroamphoacetate
Sodium lauroamphoacetate is a zwitterionic surfactant of the amphoacetate class. It is used as a very mild cleaning agent originally used in shampoos and body washes for infants but it now sees broader use in other personal care products.
Synthe ...
, are used in personal care products where mildness and non-irritancy are particularly important (e.g. baby products, "no more tears" shampoos etc.).
As precursors of imidazoles
Imidazole
Imidazole (ImH) is an organic compound with the formula . It is a white or colourless solid that is soluble in water, producing a mildly alkaline solution. It can be classified as a heterocycle, specifically as a diazole.
Many natural products, ...
s can be prepared from dehydrogenation of imidazolines.
Homogeneous catalysis
As a structural analogue of 2-oxazolines, 2-imidazolines have been developed asligand
In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's el ...
s in coordination chemistry. The substitutions on the nitrogen atom in the imidazoline ring provide opportunities for fine-tuning the electronic and steric properties. Some of the complexes function as catalysts for Suzuki–Miyaura couplings, Mizoroki–Heck reactions, Diels–Alder reaction
In organic chemistry, the Diels–Alder reaction is a chemical reaction between a Conjugated system, conjugated diene and a substituted alkene, commonly termed the Diels–Alder reaction#The dienophile, dienophile, to form a substituted cyclohexe ...
s, asymmetric allylic substitution An allylic rearrangement or allylic shift is an organic chemical reaction in which reaction at a center vicinal to a double bond causes the double bond to shift to an adjacent pair of atoms:
It is encountered in both nucleophilic and electrophi ...
, ,3sigmatropic rearrangement
In organic chemistry, a sigmatropic reaction () is a pericyclic reaction wherein the net result is one sigma bond (σ-bond) is changed to another σ-bond in an intramolecular reaction. In this type of rearrangement reaction, a substituent moves f ...
, Henry reaction
The Henry reaction is a classic carbon–carbon bond formation reaction in organic chemistry. Discovered in 1895 by the Belgian chemist Louis Henry (1834–1913), it is the combination of a nitroalkane and an aldehyde or ketone in the presence ...
s.
See also
*Imidazoline receptor
Imidazoline receptors are the primary receptors on which clonidine and other imidazolines act. There are three main classes of imidazoline receptor: I1 is involved in inhibition of the sympathetic nervous system to lower blood pressure, I2 has ...
* Imidazolidine
Imidazolidine is a heterocyclic compound (CH2)2(NH)2CH2. The parent imidazolidine is lightly studied, but related compounds substituted on one or both nitrogen centers are more common. Generally, they are colorless, polar, basic compounds. Imida ...
References
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