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 s ...

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 Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent ...

alkanoic acid. 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 A beta-lactam (β-lactam) ring is a four-membered lactam. A ''lactam'' is a cyclic amide, and ''beta''-lactams are named so because the nitrogen atom is attached to the Β carbon, β-carbon atom relative to the carbonyl. The simplest β-lactam p ...

(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 am ...

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 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-substituted ...

in the

Beckmann rearrangement The Beckmann rearrangement, named after the German chemist Ernst Otto Beckmann (1853–1923), is a rearrangement of an oxime functional group to substituted amides. The rearrangement has also been successfully performed on haloimines and nitrones ...

Schmidt reaction

Lactams form from cyclic ketones and hydrazoic acid in the

Schmidt reaction In organic chemistry, the Schmidt reaction is an organic reaction in which an azide reacts with a carbonyl derivative, usually an aldehyde, ketone, or carboxylic acid, under acidic conditions to give an amine or amide, with expulsion of nitrogen ...

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 ...

amino acids 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 am ...

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 substituen ...

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. Carboxylic ...

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 HATU (1- is(dimethylamino)methylene1H-1,2,3-triazolo ,5-byridinium 3-oxide hexafluorophosphate, Hexafluorophosphate Azabenzotriazole Tetramethyl Uronium) is a reagent used in peptide coupling chemistry to generate an active ester from a carboxyli ...

and

PyAOP PyAOP ((7-Azabenzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate) is a coupling reagent used in solid phase peptide synthesis. It is a derivative of the HOAt family of coupling reagents. It is preferred over HATU, because it does ...

Intramolecular nucleophilic subsitution

Lactams form from intramolecular attack of

linear acyl derivatives Linearity is the property of a mathematical relationship (''function'') that can be graphically represented as a straight line. Linearity is closely related to '' proportionality''. Examples in physics include rectilinear motion, the linear r ...

from the

nucleophilic abstraction Nucleophilic abstraction is a type of an organometallic reaction which can be defined as a nucleophilic attack on a ligand which causes part or all of the original ligand to be removed from the metal along with the nucleophile.Spessard, Gary; Mie ...

reaction.

Iodolactamization

iminium In organic chemistry, an iminium cation is a polyatomic ion with the general structure . They are common in synthetic chemistry and biology. Structure Iminium cations adopt alkene-like geometries. The central C=N unit is nearly coplanar with al ...

ion reacts with a

halonium ion A halonium ion is any onium ion containing a halogen atom carrying a positive charge. This cation has the general structure where X is any halogen and no restrictions on R, this structure can be cyclic or an open chain molecular structure. Halo ...

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 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 , and boils to a vi ...

. :

Kinugasa reaction

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

alkynes \ce \ce Acetylene \ce \ce \ce Propyne \ce \ce \ce \ce 1-Butyne In organic chemistry, an alkyne is an unsaturated hydrocarbon containing at least one carbon—carbon triple bond. The simplest acyclic alkynes with only one triple bond and no ...

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 +2cycloaddition process. This reaction is a 1,3-dipolar cycloaddition, in which the nitron ...

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 prod ...

(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 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 betwee ...

. 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 hydr ...

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 through ...

References

External links

*{{Commonscatinline, Lactams Functional groups