2-Oxazolidinone

Last updated
2-Oxazolidone
2-Oxazolidone structure.svg
Oxazolidin-2-one-3D-balls.png
Names
Preferred IUPAC name
1,3-Oxazolidin-2-one
Other names
1,3-Oxazolidin-2-one, 2-Oxo-1,3-oxazolidine, 2-Oxotetrahydro-1,3-oxazole
Identifiers
3D model (JSmol)
ChemSpider
ECHA InfoCard 100.007.129 OOjs UI icon edit-ltr-progressive.svg
KEGG
PubChem CID
UNII
  • InChI=1S/C3H5NO2/c5-3-4-1-2-6-3/h1-2H2,(H,4,5) Yes check.svgY
    Key: IZXIZTKNFFYFOF-UHFFFAOYSA-N Yes check.svgY
  • InChI=1/C3H5NO2/c5-3-4-1-2-6-3/h1-2H2,(H,4,5)
    Key: IZXIZTKNFFYFOF-UHFFFAOYAE
  • O=C1OCCN1
Properties
C3H5NO2
Molar mass 87.077 g/mol
Appearancewhite or colorless solid
Melting point 86 to 89 °C (187 to 192 °F; 359 to 362 K)
Boiling point 220 °C (428 °F; 493 K) at 48 torr
Related compounds
Related compounds
Oxazolidine
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Yes check.svgY  verify  (what is  Yes check.svgYX mark.svgN ?)

2-Oxazolidinone is a heterocyclic organic compound containing both nitrogen and oxygen in a 5-membered ring.

Contents

Synthesis and occurrence

The compound arises by the reaction of an ethanolamine and dimethylcarbonate [1] or related phosgene equivalents. [2]

It is one of waste products generated in amine gas treating due to cyclization of ethanolamine carbamate. [3]

History

The compound was first reported in 1888 by German chemist Siegmund Gabriel. While investigating reactions of bromoethylamine hydrobromide, he treated it with silver carbonate and isolated a product with melting point around 90–91°C. He determined its empirical formula correctly, but neither gave it a specific name nor studied its properties. [4]

Nine years later Gabriel returned to the topic together with G. Eschenbach, developing a more efficient synthesis using sodium bicarbonate 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. [5]

Substituted oxazolidinones

Evans auxiliaries

Oxazolidinones are useful as Evans auxiliaries, which are of interest for chiral synthesis. In a common implementation, an acid chloride substrate reacts with a chiral oxazolidinone to form an imide. Substituents at the 4 and 5 position of the oxazolidinone direct any aldol reaction to the alpha position of the carbonyl of the substrate. [6] Asymmetric Diels-Alder reactions are also enabled by these auxiliaries. [7]

Pharmaceuticals

Oxazolidinones are found in some antimicrobials. Oxazolidinones inhibit protein synthesis by interfering with the binding of N-formylmethionyl-tRNA to the ribosome. [8] (See Linezolid#Pharmacodynamics)

Some of the most important oxazolidinones are antibiotics. [9]

Examples of oxazolidinone-containing antibiotics:

Chemical structure of tedizolid Tedizolid.svg
Chemical structure of tedizolid
Chemical structure of linezolid Linezolid.svg
Chemical structure of linezolid

A first commercially available 1,3-oxazolidinone is the antibiotic linezolid.

See also

References

  1. Karl-Heinz Scholz, Hans-Georg Heine, Willy Hartmann (1984). "Synthesis and Diels–Alder Rearctions of 3-Acetyl-2(3H)-Oxazolone: 6-Amino-3,4-dimethyl-cis-3-cyclohexen-1-ol". Organic Syntheses. 62: 149. doi:10.15227/orgsyn.062.0149.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  2. T. Akiba, O. Tamura, S. Terashima (1998). "(4R,5S)-4,5-Diphenyl-3-Vinyl-2-Oxazolidinone". Organic Syntheses. 75: 45. doi:10.15227/orgsyn.075.0045.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  3. Salim, S. R. S. (2021-03-01). "Treatment of amine wastes generated in industrial processes". IOP Conference Series: Materials Science and Engineering. 1092 (1): 012051. Bibcode:2021MS&E.1092a2051S. doi: 10.1088/1757-899x/1092/1/012051 . ISSN   1757-8981.
  4. Gabriel, S. (1888). "Ueber einige Derivate des Aethylamins". Berichte der Deutschen Chemischen Gesellschaft (in German). 21 (1): 566–575. doi:10.1002/cber.188802101103. ISSN   0365-9496.
  5. Gabriel, S.; Eschenbach, G. (September 1897). "Notizen über Bromäthylamin und Vinylamin" . Berichte der Deutschen Chemischen Gesellschaft (in German). 30 (3): 2494–2497. doi:10.1002/cber.18970300324. ISSN   0365-9496.
  6. James R. Gage, David A. Evans (1990). "Diastereoselective Aldol Condensation Using a Chiral Oxazolidinone Auxiliary: (2S,3S)-3-Hydroxy-3-Phenyl-2-Methylpropanoic Acid". Organic Syntheses. 68: 83. doi:10.15227/orgsyn.068.0083.
  7. S. Pikul, E. J. Corey (1993). "Enantioselective, Catlytic Diels-Alder Reaction: (1S-endo)-3-(Bicyclo[2.2.1]Hept-5-en-2-ylcarbonyl)-2-Oxazolidinone". Organic Syntheses. 71: 30. doi:10.15227/orgsyn.071.0030.
  8. Shinabarger, D. (1999). "Mechanism of action of the oxazolidinone antibacterial agents". Expert Opinion on Investigational Drugs. 8 (8): 1195–1202. doi:10.1517/13543784.8.8.1195. PMID   15992144.
  9. Sonia Ilaria Maffioli (2014). "A Chemist's Survey of Different Antibiotic Classes". In Claudio O. Gualerzi; Letizia Brandi; Attilio Fabbretti; Cynthia L. Pon (eds.). Antibiotics: Targets, Mechanisms and Resistance. Wiley-VCH. ISBN   9783527659685.
  10. Wookey, A.; Turner, P. J.; Greenhalgh, J. M.; Eastwood, M.; Clarke, J.; Sefton, C. (2004). "AZD2563, a novel oxazolidinone: definition of antibacterial spectrum, assessment of bactericidal potential and the impact of miscellaneous factors on activity in vitro". Clinical Microbiology and Infection. 10 (3): 247–254. doi: 10.1111/j.1198-743X.2004.00770.x . PMID   15008947.
  11. "Rx 1741". Rib-X Pharmaceuticals. 2009. Archived from the original on 2009-02-26. Retrieved 2009-05-17.
  12. Gordeev, Mikhail F.; Yuan, Zhengyu Y. (2014). "New Potent Antibacterial Oxazolidinone (MRX-I) with an Improved Class Safety Profile". Journal of Medicinal Chemistry. 57 (11): 4487–4497. doi:10.1021/jm401931e. PMID   24694071.
  13. Zhao, Xu; Huang, Haihui; Yuan, Hong; Yuan, Zhengyu; Zhang, Yingyuan (2022). "A Phase III multicentre, randomized, double-blind trial to evaluate the efficacy and safety of oral contezolid versus linezolid in adults with complicated skin and soft tissue infections". Journal of Antimicrobial Chemotherapy. 77 (6): 1762–1769. doi:10.1093/jac/dkac073. PMID   35265985.
  14. Hoy, Sheridan M. (2021). "Contezolid: First Approval". Drugs. 81 (13): 1587–1591. doi:10.1007/s40265-021-01576-0. PMC   8536612 . PMID   34365606.
  15. "China NMPA Approves MicuRx's Contezolid for Treatment of Drug-Resistant Bacterial Infection – MicuRx Pharmaceuticals, Inc".
  16. ClinicalTrials.gov Identifier: NCT05369052