lactams
Summary
A lactam is a cyclic amide: the N–C=O group sits inside a ring. It forms when an amino acid's amine attacks its own carboxyl group and water is lost. Ring size is named by Greek letter (β = 4-membered, γ = 5, δ = 6), and the strained β-lactam is more reactive than an ordinary amide.
Detail
Meaning: A lactam is a cyclic amide: the nitrogen and the carbonyl carbon are both part of the same ring. It forms by intramolecular nucleophilic acyl substitution, when the amine of an amino acid attacks its own carboxyl group and water is lost. The Greek letter names the carbon that carries the nitrogen, which sets the ring size: β gives a four-membered ring, γ five, δ six. Five- and six-membered rings form most readily because they have little ring strain. Lactams are the nitrogen analogs of lactones, which are cyclic esters.
On the MCAT: Expect to identify a lactam in a drawn structure, state its ring size, or predict the product when a γ- or δ-amino acid cyclizes. Hydrolysis with aqueous acid or base opens the ring and returns the amino acid (or its salt). Penicillin-type β-lactams may appear as an example of a strained ring: angle strain in the four-membered ring makes the carbonyl more reactive toward nucleophiles than an ordinary amide.
Common confusion: Lactam versus lactone. A lactam has N–C=O in the ring; a lactone has O–C=O. Also, a β-lactam is a four-membered ring, not five. Count the nitrogen and the carbonyl carbon as ring atoms.
Sources
- Organic Chemistry (Clayden, Greeves, Warren)
- Organic Chemistry (Wade)
- Organic Chemistry (Klein)
Written for the MCAT and checked before it was published. For study reference only. Spotted an error? Let us know.