2-Azetidinone

2-Azetidinone
Names
IUPAC name
2-Azetidinone
Other names
β-Propiolactam; Azetidin-2-one; 2-Azacyclobutanone
Identifiers
3D model (JSmol)
ChemSpider
ECHA InfoCard 100.156.473 Edit this at Wikidata
  • InChI=1S/C3H5NO/c5-3-1-2-4-3/h1-2H2,(H,4,5)
    Key: MNFORVFSTILPAW-UHFFFAOYSA-N
  • C1CNC1=O
Properties
C3H5NO
Molar mass 71.079 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

2-Azetidinone is a chemical compound with the molecular formula C3H5NO. It is the simplest β-lactam and it forms the central core structure of the β-lactam antibiotics and certain cholesterol medications.

Chemical structure

The molecular structure of 2-azetidinone features a highly strained four membered ring containing three carbon atoms and a nitrogen atom, with a carbonyl oxygen which is double bonded to the carbon position adjacent to the heteroatom. Because of the significant ring strain inherent to a four-membered geometry, the amide bond within 2-azetidinone is considerably more reactive toward nucleophilic attack than a typical acyclic amide.

Synthesis

The synthesis of 2-azetidinone is primarily achieved through ring-closure reactions. The Staudinger synthesis, a [2+2] cycloaddition, reacts an imine with a ketene to form the four-membered core. The Gilman-Speeter reaction provides an alternative, using a Reformatsky reagent to achieve cyclization.

Reactivity

The molecule’s reactivity is driven by its severe ring strain of approximately 26 kcal/mol. This strain prevents the nitrogen lone pair from fully delocalizing into the carbonyl group, rendering the carbonyl carbon highly electrophilic and susceptible to nucleophilic attack.

Medical applications

The 2-azetidinone ring is the primary pharmacophore in β-lactam antibiotics, including penicillins, cephalosporins, and carbapenems. These compounds function by binding to bacterial transpeptidase enzymes, effectively inhibiting cell wall synthesis. Additionally, the derivative Ezetimibe utilizes the 2-azetidinone scaffold to inhibit intestinal cholesterol absorption.

References

  1. ↑ PubChem. "2-Azetidinone". pubchem.ncbi.nlm.nih.gov. Retrieved 2026-05-22.
  2. 1 2 3 Cordero, F. M.; Giomi, D.; Machetti, F. (2024). "Synthesis of 2-Azetidinones via Cycloaddition Approaches: An Update". Reactions. 5 (3): 492–566. doi:10.3390/reactions5030026.
  3. ↑ Jarrahpour, A.; Zarei, M. (2007). "Synthesis of Novel N-(4-Ethoxyphenyl) Azetidin-2-ones and Their Oxidative N-Deprotection by Ceric Ammonium Nitrate". Molecules. 12 (10): 2364–2379. doi:10.3390/12102364. PMC 6149079. PMID 17978763.