Beta-lactam
A beta-lactam (β-lactam) ring is a four-membered lactam.[1] A lactam is a cyclic amide, and beta-lactams are named so because the nitrogen atom is attached to the β-carbon atom relative to the carbonyl. The simplest β-lactam possible is 2-azetidinone. β-lactams are significant structural units of medicines as manifested in many β-lactam antibiotics.[2] Up to 1970, most β-lactam research was concerned with the penicillin and cephalosporin groups, but since then, a wide variety of structures have been described.[3][4]
This article is about the chemical compound. For the related antibiotics, see β-Lactam antibiotic.Reactions[edit]
Due to ring strain, β-lactams are more readily hydrolyzed than linear amides or larger lactams. This strain is further increased by fusion to a second ring, as found in most β-lactam antibiotics. This trend is due to the amide character of the β-lactam being reduced by the aplanarity of the system. The nitrogen atom of an ideal amide is sp2-hybridized due to resonance, and sp2-hybridized atoms have trigonal planar bond geometry. As a pyramidal bond geometry is forced upon the nitrogen atom by the ring strain, the resonance of the amide bond is reduced, and the carbonyl becomes more ketone-like. Nobel laureate Robert Burns Woodward described a parameter h as a measure of the height of the trigonal pyramid defined by the nitrogen (as the apex) and its three adjacent atoms. h corresponds to the strength of the β-lactam bond with lower numbers (more planar; more like ideal amides) being stronger and less reactive.[15] Monobactams have h values between 0.05 and 0.10 angstroms (Å). Cephems have h values in of 0.20–0.25 Å. Penams have values in the range 0.40–0.50 Å, while carbapenems and clavams have values of 0.50–0.60 Å, being the most reactive of the β-lactams toward hydrolysis.[16]