A lactam is a
cyclic amide
In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a chemical compound, compound with the general formula , where R, R', and R″ represent any group, typically organyl functional group, groups or hydrogen at ...
, formally derived from an
amino
In chemistry, amines (, ) are organic compounds that contain carbon-nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of elec ...
alkanoic acid through
cyclization
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 ...
reactions. The term is a
portmanteau
In linguistics, a blend—also known as a blend word, lexical blend, or portmanteau—is a word formed by combining the meanings, and parts of the sounds, of two or more words together. of the words ''
lactone
Lactones are cyclic carboxylic esters. They are derived from the corresponding hydroxycarboxylic acids by esterification. They can be saturated or unsaturated.
Lactones are formed by lactonization, the intramolecular esterification of the corresp ...
'' + ''
amide
In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a chemical compound, compound with the general formula , where R, R', and R″ represent any group, typically organyl functional group, groups or hydrogen at ...
''.
Nomenclature
Greek prefixes in alphabetical order indicate ring size.
This ring-size nomenclature stems from the fact that
hydrolysis
Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution reaction, substitution, elimination reaction, elimination, and solvation reactions in which water ...
of an α-lactam gives an α-
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...
and that of a β-Lactam gives a β-amino acid, and so on.
Synthesis
General synthetic methods are used for the
organic synthesis
Organic synthesis is a branch of chemical synthesis concerned with the construction of organic compounds. Organic compounds are molecules consisting of combinations of covalently-linked hydrogen, carbon, oxygen, and nitrogen atoms. Within the gen ...
of lactams.
Beckmann rearrangement
Lactams form by the
acid-catalyzed rearrangement of
oximes
In organic chemistry, an oxime is an 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 reaction, rearrangement of an oxime functional group to substituted amides. The rearrangement has also been successfully performed on ...
.
Schmidt reaction
Lactams form from
cyclic ketones
In organic chemistry, a ketone is an organic compound with the structure , where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group (a carbon-oxygen double bond C=O). The simplest ketone is acetone ( ...
and
hydrazoic acid
Hydrazoic acid, also known as hydrogen azide, azic acid or azoimide, This also contains a detailed description of the contemporaneous production process. is a compound with the chemical formula . It is a colorless, volatile, and explosive liquid ...
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
A cyclic compound (or ring compound) is a term for a chemical compound, compound in the field of chemistry in which one or more series of atoms in the compound is connected to form a ring (chemistry), ring. Rings may vary in size from three to man ...
of
amino acids
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the Proteinogenic amino acid, 22 α-amino acids incorporated into p ...
via the coupling between an
amine
In chemistry, amines (, ) are organic compounds that contain carbon-nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of elec ...
and a
carboxylic acid
In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an Substituent, R-group. The general formula of a carboxylic acid is often written as or , sometimes as with R referring to an organyl ...
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
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; Miess ...
reaction.
Iodolactamization
An
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 a ...
ion reacts with a
halonium ion formed in situ by reaction of an
alkene
In organic chemistry, an alkene, or olefin, is a hydrocarbon containing a carbon–carbon double bond. The double bond may be internal or at the terminal position. Terminal alkenes are also known as Alpha-olefin, α-olefins.
The Internationa ...
with
iodine
Iodine is a chemical element; it has symbol I and atomic number 53. The heaviest of the stable halogens, it exists at standard conditions as a semi-lustrous, non-metallic solid 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 the
Kinugasa reaction
Diels-Alder reaction
Diels-Alder reaction between
cyclopentadiene
Cyclopentadiene is an organic compound with the chemical formula, formula C5H6. It is often abbreviated CpH because the cyclopentadienyl anion is abbreviated Cp−.
This colorless liquid has a strong and unpleasant odor. At room temperature, ...
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.]
:
Lactam–lactim tautomerism
A lactim is a cyclic
imidic 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 betw ...
. They are formed when lactams undergo
tautomer
In chemistry, 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 reloca ...
ization.
:
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 throug ...
s.
See also
*
Lactone
Lactones are cyclic carboxylic esters. They are derived from the corresponding hydroxycarboxylic acids by esterification. They can be saturated or unsaturated.
Lactones are formed by lactonization, the intramolecular esterification of the corresp ...
, a cyclic
ester
In chemistry, an ester is a compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds contain a distin ...
.
*
β-Lactam
*
β-Lactam antibiotics, which includes
penicillin
Penicillins (P, PCN or PEN) are a group of beta-lactam antibiotic, β-lactam antibiotics originally obtained from ''Penicillium'' Mold (fungus), moulds, principally ''Penicillium chrysogenum, P. chrysogenum'' and ''Penicillium rubens, P. ru ...
s
*
2-Pyrrolidone
*
2-Piperidinone 2-Piperidinone (2-piperidone or δ-valerolactam) is an organic compound with the formula . Valerolactam is formed by dehydrogenation of 5-amino-1-pentanol, catalyzed by rhodium and ruthenium complexes, The compound, a colorless solid, is classifi ...
*
Caprolactam
Caprolactam (CPL) is an organic compound with the chemical formula, formula (CH2)5C(O)NH. This colourless solid is a lactam (a cyclic amide) of caproic acid. Global demand for this compound is approximately five million tons per year, and the vast ...
References
External links
*
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Functional groups