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 soc ...
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 ...
portmanteau
A portmanteau word, or portmanteau (, ) is a blend of wordslactone'' + ''
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 ...
''.
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
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 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 ...
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 ...
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
Hydrazoic acid, also known as hydrogen azide 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 at room tem ...
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 al ...
of
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 n ...
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 re ...
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 ...
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. Haloni ...
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 ...
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 ...
cyclopentadiene
Cyclopentadiene is an organic compound with the chemical formula, formula C5H6.LeRoy H. Scharpen and Victor W. Laurie (1965): "Structure of cyclopentadiene". ''The Journal of Chemical Physics'', volume 43, issue 8, pages 2765-2766. It is often ab ...
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.
:
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 hydr ...
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 through ...
ester
In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ar ...
.
*
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 ...
penicillin
Penicillins (P, PCN or PEN) are a group of β-lactam antibiotics originally obtained from ''Penicillium'' moulds, principally '' P. chrysogenum'' and '' P. rubens''. Most penicillins in clinical use are synthesised by P. chrysogenum using ...
2-Piperidinone
2-Piperidinone (2-piperidone or δ-valerolactam) is a chemical compound classified as a lactam
A lactam is a cyclic amide, formally derived from an amino alkanoic acid. The term is a portmanteau of the words ''lactone'' + ''amide''.
Nomenclatur ...
*
Caprolactam
Caprolactam (CPL) is an organic compound with the 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 majority is used ...