A lactam is a Cyclic compound 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.
|
| 3 | α-Lactam | Aziridin-2-one | α-Acetolactam | |
| 4 | β-Lactam | Azetidin-2-one | β-Propiolactam | |
| 5 | γ-Lactam | Pyrrolidin-2-one | | |
| 6 | δ-Lactam | Piperidin-2-one | | |
| 7 | ε-Lactam | Azepan-2-one | | |
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 catalysis 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
Caprolactam, 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).
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.
[Spencer Knapp, Frank S. Gibson Organic Syntheses, Coll. Vol. 9, p.516 ( 1998); Vol. 70, p.101 ( 1992) Online article]
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[Singh, R.; Vince, R. Chem. Rev. 2012, 112 (8), pp 4642–4686."2-Azabicyclo2.2.1hept-5-en-3-one: Chemical Profile of a Versatile Synthetic Building Block and its Impact on the Development of Therapeutics"] is obtained.
[Pham, P.-T.; Vince, R. Phosphorus, Sulphur and Silicon 2007, 779-791.]
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
.
Reactions
-
Lactams can polymerize to .
See also
External links
