A lactam is a cyclic

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 is ...

, formally derived from an

amino 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 Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent su ...

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. Carboxyl ...

. The term is a

portmanteau A portmanteau word, or portmanteau (, ) is a blend of wordslactone Lactones are cyclic carboxylic esters, containing a 1-oxacycloalkan-2-one structure (), or analogues having unsaturation or heteroatoms replacing one or more carbon atoms of the ring. Lactones are formed by intramolecular esterification of the co ...

'' + ''

''.

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 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 Organic synthesis is a special branch of chemical synthesis and is concerned with the intentional construction of organic compounds. Organic molecules are often more complex than inorganic compounds, and their synthesis has developed into one o ...

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 catal ...

rearrangement of oximes 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 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 su ...

and a

carboxylic 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. Carboxyl ...

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 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, an ...

with

iodine Iodine is a chemical element with the Symbol (chemistry), symbol I and atomic number 53. The heaviest of the stable halogens, it exists as a semi-lustrous, non-metallic solid at standard conditions that melts to form a deep violet liquid at , ...

. :

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 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 Carboximidates (or more general imidates) are organic compounds, which can be thought of as esters formed between a carboximidic acid (R-C(=NR')OH) and an alcohol, with the general formula R-C(=NR')OR". They are also known as imino ethers, si ...

compound characterized by an endocyclic carbon-nitrogen

double bond In chemistry, a double bond is a covalent bond between two atoms involving four bonding electrons as opposed to two in a single bond. Double bonds occur most commonly between two carbon atoms, for example in alkenes. Many double bonds exist betw ...

. 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 hyd ...

ization. : Lactam-Lactim-Tautomerie