Lactam

From left to right, the above are general structures of βべーた-lactam, a γがんま-lactam, a δでるた-lactam, and εいぷしろん-lactam. Their common names are βべーた-propiolactam, γがんま-butyrolactam, δでるた-valerolactam, and εいぷしろん-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あるふぁ-Lactam	Aziridin-2-one	αあるふぁ-Acetolactam
4	βべーた-Lactam	Azetidin-2-one	βべーた-Propiolactam
5	γがんま-Lactam	Pyrrolidin-2-one	γがんま-Butyrolactam 2-Pyrrolidone
6	δでるた-Lactam	Piperidin-2-one	δでるた-Valerolactam 2-Piperidinone 2-piperidone
7	εいぷしろん-Lactam	Azepan-2-one	εいぷしろん-Caprolactam Caprolactam

This ring-size nomenclature stems from the fact that hydrolysis of an αあるふぁ-lactam gives an αあるふぁ-amino acid and that of a βべーた-Lactam gives a βべーた-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いぷしろん - 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がんま-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がんま-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べーた- as well as γがんま-lactam. At lower temp (−78 °C), βべーた-lactam is the preferred product. At optimum temperatures, a highly useful γがんま-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べーた-Lactam
• βべーた-Lactam antibiotics, which includes penicillins
• 2-Pyrrolidone
• 2-Piperidinone
• Caprolactam

External links

• Media related to Lactams at Wikimedia Commons