Lactam


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

Nomenclature

es in alphabetical order indicate ring size.
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. Cyclohexanone with hydrazoic acid, forms ε - Caprolactum, which upon treatment with excess acid forms Cardiazole, a heart stimulant.

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-OH, although its side-chain amine is sterically protected by extremely bulky 4-Methyltrityl 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.

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

between cyclopentadiene and chlorosulfonyl isocyanate can be utilized to obtain both β- as well as γ-lactam. At lower temp, 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.

Reactions

  • Lactams can polymerize to polyamides.