Lactam

A lactam is a cyclic amide, formally derived from an amino carboxylic acid through cyclization reactions.[1] The term is a portmanteau of the words lactone \+ amide.

## Contents

* 1 Nomenclature
* 2 Synthesis
* 2.1 Beckmann rearrangement
* 2.2 Schmidt reaction
* 2.3 Cyclization of amino acids
* 2.4 Intramolecular nucleophilic substitution
* 2.5 Iodolactamization
* 2.6 Kinugasa reaction
* 2.7 Diels-Alder reaction
* 3 Lactam–lactim tautomerism
* 4 Reactions
* 5 See also
* 6 References
* 7 External links

## 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  | 100px
4  | β-Lactam  | Azetidin-2-one  | β-Propiolactam  | 100px
5  | γ-Lactam  | Pyrrolidin-2-one  |

* γ-Butyrolactam
* 2-Pyrrolidone

| 100px
6  | δ-Lactam  | Piperidin-2-one  |

* δ-Valerolactam
* 2-Piperidinone
* 2-piperidone

| 100px
7  | ε-Lactam  | Azepan-2-one  |

* ε-Caprolactam
* Caprolactam

| 100px

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(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).[2]

### 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.[3]

### 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[4] is obtained.[5]

## 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

## References

1. ↑ IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book") (1997). Online corrected version:  (2006-) "Lactams". doi:10.1351/goldbook.L03435
2. ↑ Lam, Pak-Lun; Wu, Yue; Wong, Ka-Leung (30 March 2022). "Incorporation of Fmoc-Dab(Mtt)-OH during solid-phase peptide synthesis: a word of caution" (in en). Organic & Biomolecular Chemistry 20 (13): 2601–2604. doi:10.1039/D2OB00070A. ISSN 1477-0539. PMID 35258068. https://pubs.rsc.org/en/content/articlelanding/2022/ob/d2ob00070a.
3. ↑ Spencer Knapp, Frank S. Gibson Organic Syntheses, Coll. Vol. 9, p.516 (1998); Vol. 70, p.101 (1992) Online article
4. ↑ Singh, R.; Vince, R. Chem. Rev. 2012, 112 (8), pp 4642–4686."2-Azabicyclo[2.2.1]hept-5-en-3-one: Chemical Profile of a Versatile Synthetic Building Block and its Impact on the Development of Therapeutics"
5. ↑ Pham, P.-T.; Vince, R. Phosphorus, Sulphur and Silicon 2007, 779-791.

## External links

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