A lactam is a

cyclic Cycle, cycles, or cyclic may refer to: Anthropology and social sciences * Cyclic history, a theory of history * Cyclical theory, a theory of American political history associated with Arthur Schlesinger, Sr. * Social cycle, various cycles in so ...

amide In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it i ...

, formally derived from an amino

alkanoic acid In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxyli ...

. The term is a

portmanteau A portmanteau word, or portmanteau (, ) is a blend of wordslactone'' + ''

''.

Nomenclature

Greek prefixes in alphabetical order indicate ring size: * α-Lactam (3-atom rings) * β-Lactam (4-atom rings) * γ-Lactam (5-atom rings) * δ-Lactam (6-atom rings) * ε-Lactam (7-atom rings) This ring-size nomenclature stems from the fact that a

hydrolyzed Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile. Biological hydrolysis ...

α-Lactam leads to an α-

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...

and a β-Lactam to a β-amino acid, ''etc''.

Synthesis

General synthetic methods exist for the organic synthesis of lactams.

Beckmann rearrangement

Lactams form by the

acid-catalyzed In acid catalysis and base catalysis, a chemical reaction is catalyzed by an acid or a base. By Brønsted–Lowry acid–base theory, the acid is the proton (hydrogen ion, H+) donor and the base is the proton acceptor. Typical reactions catalyzed ...

rearrangement of

oximes In organic chemistry, an oxime is a organic compound belonging to the imines, with the general formula , where R is an organic side-chain and R’ may be hydrogen, forming an aldoxime, or another organic group, forming a ketoxime. O-substitute ...

in the Beckmann rearrangement.

Schmidt reaction

Lactams form from

cyclic ketones In organic chemistry, a ketone is a functional group with the structure R–C(=O)–R', where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group –C(=O)– (which contains a carbon-oxygen double bon ...

and hydrazoic acid in the Schmidt reaction.

Cyclization of amino acids

Lactams can be formed from

cyclisation A cyclic compound (or ring compound) is a term for a compound in the field of chemistry in which one or more series of atoms in the compound is connected to form a ring. Rings may vary in size from three to many atoms, and include examples where a ...

of amino acids via the coupling between an

amine In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent ...

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 Couple or couples may refer to : Basic meaning *Couple (app), a mobile app which provides a mobile messaging service for two people *Couple (mechanics), a system of forces with a resultant moment but no resultant force *Couple (relationship), tw ...

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 subsitution

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 In organic chemistry, an alkene is a hydrocarbon containing a carbon–carbon double bond. Alkene is often used as synonym of olefin, that is, any hydrocarbon containing one or more double bonds.H. Stephen Stoker (2015): General, Organic ...

with iodine. :

Kinugasa reaction

Lactams form by copper-catalyzed 1,3-dipolar cycloaddition of alkynes and

nitrones In organic chemistry, a nitrone is a functional group consisting of an ''N''-oxide of an imine. The general structure is , where R’ is not a hydrogen. A nitrone is a 1,3-dipole, and is used in 1,3-dipolar cycloadditions. Other reactions of n ...

in the

Kinugasa reaction The nitrone-olefin (3+2) cycloaddition reaction is the combination of a nitrone with an alkene or alkyne to generate an isoxazoline or isoxazolidine via a +2 cycloaddition process. This reaction is a 1,3-dipolar cycloaddition, in which the nitrone ...

Diels-Alder reaction

Diels-Alder reaction between cyclopentadiene and

chlorosulfonyl isocyanate Chlorosulfonyl isocyanate is the chemical compound ClSO2NCO, known as CSI. This compound is a versatile reagent in organic synthesis. Preparation, structure, handling CSI is prepared by treating cyanogen chloride with sulfur trioxide, the produc ...

(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.Pham, P.-T.; Vince, R. ''Phosphorus, Sulphur and Silicon'' 2007, 779-791. : Preparation_of_gamma_and_beta_lactams

Tautomerization to lactims

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

tautomer Tautomers () are structural isomers (constitutional isomers) of chemical compounds that readily interconvert. The chemical reaction interconverting the two is called tautomerization. This conversion commonly results from the relocation of a hy ...

ization. : Lactam-Lactim-Tautomerie

Reactions

* Lactams can polymerize to

polyamide A polyamide is a polymer with repeating units linked by amide bonds. Polyamides occur both naturally and artificially. Examples of naturally occurring polyamides are proteins, such as wool and silk. Artificially made polyamides can be made th ...

References

External links

*{{Commonscatinline, Lactams Functional groups