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2-Oxazolidinone is a
heterocyclic 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 ...
organic compound Some chemical authorities define an organic compound as a chemical compound that contains a carbon–hydrogen or carbon–carbon bond; others consider an organic compound to be any chemical compound that contains carbon. For example, carbon-co ...
containing both nitrogen and oxygen in a 5-membered ring.


Synthesis and occurrence

The compound arises by the reaction of an ethanolamine and dimethylcarbonate or related
phosgene Phosgene is an organic chemical compound with the formula . It is a toxic, colorless gas; in low concentrations, its musty odor resembles that of freshly cut hay or grass. It can be thought of chemically as the double acyl chloride analog of ...
equivalents. It is one of waste products generated in
amine gas treating Amine gas treating, also known as amine scrubbing, gas sweetening and acid gas removal, refers to a group of processes that use aqueous solutions of various Amine#Aliphatic amines, alkylamines (commonly referred to simply as amines) to remove hydr ...
due to cyclization of
ethanolamine Ethanolamine (2-aminoethanol, monoethanolamine, ETA, or MEA) is a naturally occurring organic chemical compound with the formula or . The molecule is bifunctional, containing both a primary amine and a primary alcohol. Ethanolamine is a colorl ...
carbamate.


History

The compound was first reported in 1888 by German chemist
Siegmund Gabriel Siegmund Gabriel (7 November 1851 – 22 March 1924) was a German chemist. Scientific career Siegmund Gabriel began studying chemistry at the University of Berlin in 1871. He continued his studies at the University of Heidelberg in 1872 wi ...
. While investigating reactions of bromoethylamine hydrobromide, he treated it with
silver carbonate Silver carbonate is the chemical compound with the formula Ag2 C O3. This salt is yellow but typical samples are grayish due to the presence of elemental silver. It is poorly soluble in water, like most transition metal carbonates. Preparation a ...
and isolated a product with melting point around 90–91°C. He determined its empirical formula correctly, but neither gave it a specific name not studied its properties. Nine years later Gabriel returned to the topic together with G. Eschenbach, developing a more efficient synthesis using
sodium bicarbonate Sodium bicarbonate ( IUPAC name: sodium hydrogencarbonate), commonly known as baking soda or bicarbonate of soda (or simply “bicarb” especially in the UK) is a chemical compound with the formula NaHCO3. It is a salt composed of a sodium cat ...
instead of the silver salt. They referred to the compound as "Oxäthylcarbaminsäureanhydrid" (hydroxyethylcarbamic acid anhydride), recognizing its relationship to ethanolamine and its cyclic structure. Their 1897 paper focused on optimizing the yield of oxazolidone and investigating some of its reactions, such as its conversion to 1-(2-hydroxyethyl)-3-phenylurea upon treatment with aniline.


Substituted oxazolidinones


Evans auxiliaries

Oxazolidinones are useful as Evans auxiliaries, which are of interest for
chiral synthesis Enantioselective synthesis, also called asymmetric synthesis, is a form of chemical synthesis. It is defined by IUPAC as "a chemical reaction (or reaction sequence) in which one or more new elements of chirality are formed in a substrate molecul ...
. In a common implementation, an
acid chloride In organic chemistry, an acyl chloride (or acid chloride) is an organic compound with the functional group . Their formula is usually written , where R is a side chain. They are reactive derivatives of carboxylic acids (). A specific example o ...
substrate reacts with a chiral oxazolidinone to form an
imide In organic chemistry, an imide is a functional group consisting of two acyl groups bound to nitrogen. The compounds are structurally related to acid anhydrides, although imides are more resistant to hydrolysis. In terms of commercial applications ...
. Substituents at the 4 and 5 position of the oxazolidinone direct any
aldol reaction The aldol reaction (aldol addition) is a Chemical reaction, reaction in organic chemistry that combines two Carbonyl group, carbonyl compounds (e.g. aldehydes or ketones) to form a new β-hydroxy carbonyl compound. Its simplest form might invol ...
to the alpha position of the carbonyl of the substrate. Asymmetric Diels-Alder reactions are also enabled by these auxiliaries.


Pharmaceuticals

Oxazolidinones are found in some antimicrobials. Oxazolidinones inhibit protein synthesis by interfering with the binding of N-formylmethionyl-tRNA to the ribosome. (See Linezolid#Pharmacodynamics) Some of the most important oxazolidinones are antibiotics. Examples of oxazolidinone-containing antibiotics: *
Linezolid Linezolid is an antibiotic used for the treatment of infections caused by Gram-positive bacteria that are resistant to other antibiotics. Linezolid is active against most Gram-positive bacteria that cause disease, including streptococci, va ...
(Zyvox), which is available for
intravenous Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...
administration and also has the advantage of having excellent oral
bioavailability In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. H ...
. *
Posizolid Posizolid is an oxazolidinone antibiotic under investigation by AstraZeneca for the treatment of bacterial infections. At a concentration of 2 mg/L it inhibited 98% of all Gram-positive bacteria tested in vitro ''In vitro'' (meaning '' ...
, which appears to have excellent, targeted bactericidal activity against all common gram-positive bacteria, regardless of resistance to other classes of antibiotics. *
Tedizolid Tedizolid, sold under the brand name Sivextro (by Merck) is an oxazolidinone-class antibiotic. Tedizolid phosphate is a phosphate ester prodrug of the active compound tedizolid. It was developed by Cubist Pharmaceuticals, following acquisition of ...
, (Sivextro) which is approved for acute skin infections *
Radezolid Radezolid (INN, codenamed RX-1741) is a novel oxazolidinone The oxazolidones and isoxazolidones are a set of six isomeric five-membered heterocyclic compounds consisting of a carbonyl group, an oxygen atom, a nitrogen atom with a hydrogen atom at ...
(RX-1741) has completed some phase-II clinical trials. *
Contezolid Contezolid (trade name Youxitai) is an antibiotic of the oxazolidinone class. It is effective against ''Staphylococcus aureus'', methicillin-resistant ''Staphylococcus aureus'' (MRSA), ''Streptococcus pyogenes'', ''Streptococcus agalactiae'', a ...
(MRX-I) has reported phase 1 data and phase III data. In 2021, a new drug summary was published by ADIS Press. In June 2021, marketing approval was granted by the Chinese National Medical Products Administration (NMPA) for use of oral contezolid in moderate to severe complicated skin and skin structure infections. In June 2022, contezolid oral tablets and contezolid acefosamil IV (a prodrug of contezolid) began Phase 3 global clinical trials in moderate to severe diabetic foot infections.ClinicalTrials.gov Identifier: NCT05369052 An additional global Phase 3 study is planned for acute bacterial skin and skin structure infections (ABSSSI) for the combination of contezolid and contezolid acefosamil. * An oxazolidinone derivative used for other purposes is
rivaroxaban Rivaroxaban, sold under the brand name Xarelto among others, is an anticoagulant medication (blood thinner) used to treat and reduce the risk of blood clots. Specifically it is used to treat deep vein thrombosis and pulmonary emboli and prev ...
, which is approved by the U.S. FDA for venous thromboembolism prophylaxis. A first commercially available 1,3-oxazolidinone is the antibiotic
linezolid Linezolid is an antibiotic used for the treatment of infections caused by Gram-positive bacteria that are resistant to other antibiotics. Linezolid is active against most Gram-positive bacteria that cause disease, including streptococci, va ...
.


See also

*
Oxazolidine Oxazolidine is a five-membered heterocycle ringwith the formula .The O atom and NH groups are not mutually bonded, in contrast to isoxazolidine. Oxazolidines (emphasis on plural) are derivatives of the parent oxazolidine owing to the presence of ...
– the ring without the carbonyl group *
Oxazolone Oxazolone is a chemical compound and functional group, with the molecular formula C3H3NO2. It was named in-line with the Hantzsch–Widman nomenclature and is part of a large family of oxazole based compounds. There are a total of 5 structural isom ...
– the unsaturated analogues


References


External links


Synthesis of Oxazolidinones – Recent Literature
{{DEFAULTSORT:Oxazolidone, 2- Oxazolidinones 2-Oxazolidinones