Chemistry:Lactam

Short description: Cyclic amide

From left to right, the above are general structures of β-lactam, a γ-lactam, a δ-lactam, and ε-lactam. Their common names are β-propiolactam, γ-butyrolactam, δ-valerolactam, and ε-caprolactam.

A lactam is a cyclic amide, formally derived from an amino alkanoic acid through cyclization reactions. The term is a portmanteau of the words lactone + amide.

Nomenclature

Greek prefixes in alphabetical order indicate ring size.

Ring size (number of atoms in the ring)	Systematic name	IUPAC name	Common name(s)	Structure
3	α-Lactam	Aziridin-2-one	α-Acetolactam
4	β-Lactam	Azetidin-2-one	β-Propiolactam
5	γ-Lactam	Pyrrolidin-2-one	γ-Butyrolactam 2-Pyrrolidone
6	δ-Lactam	Piperidin-2-one	δ-Valerolactam 2-Piperidinone 2-piperidone
7	ε-Lactam	Azepan-2-one	ε-Caprolactam Caprolactam

This ring-size nomenclature stems from the fact that hydrolysis of an α-lactam gives an α-amino acid and that of a β-Lactam gives a β-amino acid, and so on.

Synthesis

General synthetic methods are used for the organic synthesis of lactams.

Beckmann rearrangement

Lactams form by the acid-catalyzed rearrangement of oximes in the Beckmann rearrangement.

Schmidt reaction

Lactams form from cyclic ketones and hydrazoic acid in the Schmidt reaction.

Cyclization of amino acids

Lactams can be formed from cyclisation of amino acids via the coupling between an amine and a carboxylic acid within the same molecule. Lactamization is most efficient in this way if the product is a γ-lactam. For example, Fmoc-Dab(Mtt)-OH, although its side-chain amine is sterically protected by extremely bulky 4-Methyltrityl (Mtt) group, the amine can still intramolecularly couple with the carboxylic acid to form a γ-lactam. This reaction almost finished within 5 minutes with many coupling reagents (e.g. HATU and PyAOP).

Intramolecular nucleophilic substitution

Lactams form from intramolecular attack of linear acyl derivatives from the nucleophilic abstraction reaction.

Iodolactamization

An iminium ion reacts with a halonium ion formed in situ by reaction of an alkene with iodine.

Kinugasa reaction

Lactams form by copper-catalyzed 1,3-dipolar cycloaddition of alkynes and nitrones in the Kinugasa reaction

Diels-Alder reaction

Diels-Alder reaction between cyclopentadiene and chlorosulfonyl isocyanate (CSI) can be utilized to obtain both β- as well as γ-lactam. At lower temp (−78 °C), β-lactam is the preferred product. At optimum temperatures, a highly useful γ-lactam known as Vince Lactam is obtained.

Lactam–lactim tautomerism

A lactim is a cyclic imidic acid compound characterized by an endocyclic carbon-nitrogen double bond. They are formed when lactams undergo tautomerization.

   Lactam                                                    Lactim

Reactions

• Lactams can polymerize to polyamides.

See also

• Lactone, a cyclic ester.
• β-Lactam
• β-Lactam antibiotics, which includes penicillins
• 2-Pyrrolidone
• 2-Piperidinone
• Caprolactam