Lactones are cyclic carboxylic esters are intramolecular esters derived from hydroxy carboxylic acids. They can be saturated or unsaturated. Some contain heteroatoms replacing one or more carbon atoms of the ring. [1]
Lactones are formed by intramolecular esterification of the corresponding hydroxycarboxylic acids, which takes place spontaneously when the ring that is formed is five- or six-membered. Lactones with three- or four-membered rings (α-lactones and β-lactones) are very reactive, making their isolation difficult. Special methods are normally required for the laboratory synthesis of small-ring lactones as well as those that contain rings larger than six-membered. [2]
Greek prefixes in alphabetical order indicate ring size.
Ring size (number of atoms in the ring) | Systematic name | IUPAC name | Common name (s) | Structure |
---|---|---|---|---|
3 | α-lactone | Oxiran-2-one | Acetolactone | |
4 | β-lactone | Oxetan-2-one |
| |
5 | γ-lactone | Oxolan-2-one | γ-Butyrolactone | |
6 | δ-lactone | Oxan-2-one | ||
7 | ε-lactone | Oxepan-2-one |
|
Lactones are usually named according to the precursor acid molecule (aceto = 2 carbon atoms, propio = 3, butyro = 4, valero = 5, capro = 6, etc.), with a -lactone suffix and a Greek letter prefix that specifies the number of carbon atoms in the heterocycle — that is, the distance between the relevant -OH and the -COOH groups along said backbone. The first carbon atom after the carbon in the -COOH group on the parent compound is labelled α, the second will be labeled β, and so forth. Therefore, the prefixes also indicate the size of the lactone ring: α-lactone = 3-membered ring, β-lactone = 4-membered, γ-lactone = 5-membered, δ-lactone = 6-membered, etc. Macrocyclic lactones are known as macrolactones. [3]
The other suffix used to denote a lactone is -olide, used in substance class names like butenolide , macrolide , cardenolide or bufadienolide .
To obtain the preferred IUPAC names, lactones are named as heterocyclic pseudoketones by adding the suffix 'one', 'dione', 'thione', etc. and the appropriate multiplicative prefixes to the name of the heterocyclic parent hydride. [4]
The name lactone derives from the ring compound called lactide, which is formed from the dehydration of 2-hydroxypropanoic acid (lactic acid) CH3-CH(OH)-COOH. Lactic acid, in turn, derives its name from its original isolation from soured milk (Latin: lac, lactis). The name was coined in 1844 by the French chemist Théophile-Jules Pelouze, who first obtained it as a derivative of lactic acid. [5] An internal dehydration reaction within the same molecule of lactic acid would have produced alpha-propiolactone, a lactone with a 3-membered ring.
In 1880 the German chemist Wilhelm Rudolph Fittig extended the name "lactone" to all intramolecular carboxylic esters. [6]
The most stable lactones are the 5-membered γ-lactones and 6-membered δ-lactones because, as in most organic cycles, 5 and 6 membered rings minimize the strain of bond angles. β-lactones appear in a number of natural products, but are only stable in artificial conditions (i.e. a test tube). [7] α‑Lactones can be detected as transient species in mass spectrometry experiments. [8] The reactions of lactones are similar to those of esters.
Many naturally-occurring lactones are γ- and δ-lactones, both saturated and unsaturated. They contribute to the aroma of fruits, butter, cheese, and other foods.
Macrocyclic lactones are also important natural products. Cyclopentadecanolide is responsible for the musklike odor of angelica root oil. Of the naturally occurring bicyclic lactones, phthalides are responsible for the odors of celery and lovage oils, and coumarin for woodruff. [9] Lactones are present in oak wood, and they contribute to the flavour profile of barrel-aged beers. [10]
Lactone rings occur widely as building blocks in nature, such as in ascorbic acid, kavain, nepetalactone, gluconolactone, hormones (spironolactone, mevalonolactone), enzymes (lactonase), neurotransmitters (butyrolactone, avermectins), antibiotics (macrolides like erythromycin; amphotericin B), anticancer drugs (vernolepin, epothilones), phytoestrogens (resorcylic acid lactones, cardiac glycosides).
Many methods in ester synthesis can also be applied to that of lactones. Lactonization competes with polymerization for longer hydroxy acids, or the strained β‑lactones. γ‑Lactones, on the other hand, are so stable that 4-hydroxy acids (R-CH(OH)-(CH2)2-CO2H) spontaneously cyclise.
In one industrial synthesis of oxandrolone the key lactone-forming step is an organic reaction - esterification. [11] [12]
In halolactonization, an alkene is attacked by a halogen via electrophilic addition with the cationic intermediate captured intramolecularly by an adjacent carboxylic acid. [13]
Specific methods include Yamaguchi esterification, Shiina macrolactonization, Corey-Nicolaou macrolactonization, Baeyer–Villiger oxidation and nucleophilic abstraction.
The γ-lactones γ-octalactone, γ-nonalactone, γ-decalactone, γ-undecalactone can be prepared in good yield in a one-step process by radical addition of primary fatty alcohols to acrylic acid, using di-tert-butyl peroxide as a catalyst. [9]
An alternative radical reaction yielding γ-lactones is the manganese-mediated coupling.
Lactones exhibit the reactions characteristic of esters.
Heating a lactone with a base (sodium hydroxide) will hydrolyse the lactone to its parent compound, the straight chained bifunctional compound. Like straight-chained esters, the hydrolysis-condensation reaction of lactones is a reversible reaction, with an equilibrium. However, the equilibrium constant of the hydrolysis reaction of the lactone is lower than that of the straight-chained ester i.e. the products (hydroxyacids) are less favored in the case of the lactones. This is because although the enthalpies of the hydrolysis of esters and lactones are about the same, the entropy of the hydrolysis of lactones is less than the entropy of straight-chained esters. Straight-chained esters give two products upon hydrolysis, making the entropy change more favorable than in the case of lactones which gives only a single product.
Lactones also react with amines to give the ring-opened alcohol and amide.
Lactones can be reduced to diols using lithium aluminium hydride. For instance, gamma-lactones is reduced to butane-1,4-diol, (CH2(OH)-(CH2)2-CH2(OH).
Lactones readily form polyesters according to the formula, and have been shown to oligomerize without catalyst as well: [14] [15]
The double lactone called lactide polymerizes to polylactic acid (polylactide). The resulting materials, polylactic acid, have many attractive properties. [16] [17]
Lactones contribute significantly to the flavor of fruit, and of unfermented and fermented dairy products, [18] and are therefore used as flavors and fragrances. [9] Some examples are γ-decalactone (4-decanolide), which has a characteristic peach flavor; [18] δ-decalactone (5-decanolide), which has a creamy coconut/peach flavour; γ-dodecalactone (4-dodecanolide), which also has a coconut/fruity flavor, [18] a description which also fits γ-octalactone (4-octanolide), [19] although it also has a herbaceous character; [18] γ-nonalactone, which has an intense coconut flavor of this series, despite not occurring in coconut, [20] and γ-undecalactone.
Macrocyclic lactones (cyclopentadecanolide, 15-pentadec-11/12-enolide) have odors similar to macrocyclic ketones of animal origin (muscone, civetone), but they can be prepared more easily, for example, by depolymerization of the corresponding linear polyesters. Replacement of a methylene unit by oxygen barely affects the odor of these compounds, and oxalactones with 15 – 17-membered rings are produced in addition to cyclopentadecanolide (e. g., 12-oxa-16-hexadecanolide). [9]
Prebiotically plausible lactones, such as ε-caprolactone and δ-valerolactone, have been shown to oligomerize without the usage of catalysts forming oligomers that may have been relevant during the origin of life. [21]
Polycaprolactone is an important plastic.
In chemistry, an ester is a compound derived from an acid in which the hydrogen atom (H) of at least one acidic hydroxyl group of that acid is replaced by an organyl group. Analogues derived from oxygen replaced by other chalcogens belong to the ester category as well. According to some authors, organyl derivatives of acidic hydrogen of other acids are esters as well, but not according to the IUPAC.
In organic chemistry, a ketone is an organic compound 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)−. The simplest ketone is acetone, with the formula (CH3)2CO. Many ketones are of great importance in biology and in industry. Examples include many sugars (ketoses), many steroids, and the solvent acetone.
In organic chemistry, a ketene is an organic compound of the form RR'C=C=O, where R and R' are two arbitrary monovalent chemical groups. The name may also refer to the specific compound ethenone H2C=C=O, the simplest ketene.
In chemistry, intramolecular describes a process or characteristic limited within the structure of a single molecule, a property or phenomenon limited to the extent of a single molecule.
A diol is a chemical compound containing two hydroxyl groups. An aliphatic diol is also called a glycol. This pairing of functional groups is pervasive, and many subcategories have been identified.
In organic chemistry, a nitrile is any organic compound that has a −C≡N functional group. The name of the compound is composed of a base, which includes the carbon of the −C≡N, suffixed with "nitrile", so for example CH3CH2C≡N is called "propionitrile". The prefix cyano- is used interchangeably with the term nitrile in industrial literature. Nitriles are found in many useful compounds, including methyl cyanoacrylate, used in super glue, and nitrile rubber, a nitrile-containing polymer used in latex-free laboratory and medical gloves. Nitrile rubber is also widely used as automotive and other seals since it is resistant to fuels and oils. Organic compounds containing multiple nitrile groups are known as cyanocarbons.
In organic chemistry, the Michael reaction or Michael 1,4 addition is a reaction between a Michael donor and a Michael acceptor to produce a Michael adduct by creating a carbon-carbon bond at the acceptor's β-carbon. It belongs to the larger class of conjugate additions and is widely used for the mild formation of carbon-carbon bonds.
A lactam is a cyclic amide, formally derived from an amino alkanoic acid through cyclization reactions. The term is a portmanteau of the words lactone + amide.
Nucleophilic acyl substitution describes a class of substitution reactions involving nucleophiles and acyl compounds. In this type of reaction, a nucleophile – such as an alcohol, amine, or enolate – displaces the leaving group of an acyl derivative – such as an acid halide, anhydride, or ester. The resulting product is a carbonyl-containing compound in which the nucleophile has taken the place of the leaving group present in the original acyl derivative. Because acyl derivatives react with a wide variety of nucleophiles, and because the product can depend on the particular type of acyl derivative and nucleophile involved, nucleophilic acyl substitution reactions can be used to synthesize a variety of different products.
The Dieckmann condensation is the intramolecular chemical reaction of diesters with base to give β-keto esters. It is named after the German chemist Walter Dieckmann (1869–1925). The equivalent intermolecular reaction is the Claisen condensation. Dieckmann condensations are highly effective routes to 5-, 6-, and 7-member rings, but poor for larger rings.
ε-Caprolactone or simply caprolactone is a lactone possessing a seven-membered ring. Its name is derived from caproic acid. This colorless liquid is miscible with most organic solvents and water. It was once produced on a large scale as a precursor to caprolactam.
β-Propiolactone, often simply called propiolactone, is an organic compound with the formula CH2CH2CO2. It is a lactone family, with a four-membered ring. It is a colorless liquid with a slightly sweet odor, highly soluble in water and organic solvents. The carcinogenicity of this compound has limited its commercial applications.
The Kulinkovich reaction describes the organic synthesis of substituted cyclopropanols through reaction of esters with dialkyldialkoxytitanium reagents, which are generated in situ from Grignard reagents containing a hydrogen in beta-position and titanium(IV) alkoxides such as titanium isopropoxide. This reaction was first reported by Oleg Kulinkovich and coworkers in 1989.
6-Phosphogluconolactonase (EC 3.1.1.31, 6PGL, PGLS, systematic name 6-phospho-D-glucono-1,5-lactone lactonohydrolase) is a cytosolic enzyme found in all organisms that catalyzes the hydrolysis of 6-phosphogluconolactone to 6-phosphogluconic acid in the oxidative phase of the pentose phosphate pathway:
In organic chemistry, a homologation reaction, also known as homologization, is any chemical reaction that converts the reactant into the next member of the homologous series. A homologous series is a group of compounds that differ by a constant unit, generally a methylene group. The reactants undergo a homologation when the number of a repeated structural unit in the molecules is increased. The most common homologation reactions increase the number of methylene units in saturated chain within the molecule. For example, the reaction of aldehydes or ketones with diazomethane or methoxymethylenetriphenylphosphine to give the next homologue in the series.
Picoline refers to any of three isomers of methylpyridine (CH3C5H4N). They are all colorless liquids with a characteristic smell similar to that of pyridine. They are miscible with water and most organic solvents.
Synthetic musks are a class of synthetic aroma compounds to emulate the scent of deer musk and other animal musks. Synthetic musks have a clean, smooth and sweet scent lacking the fecal notes of animal musks. They are used as flavorings and fixatives in cosmetics, detergents, perfumes and foods, supplying the base note of many perfume formulas. Most musk fragrance used in perfumery today is synthetic.
Thiolactones are a class of heterocyclic compounds in organic chemistry. They are analogs of the more common lactones in which an oxygen atom is replaced with a sulfur atom. The sulfur atom is within the ring system and adjacent to a carbonyl group.
Shiina esterification is an organic chemical reaction that synthesizes carboxylic esters from nearly equal amounts of carboxylic acids and alcohols by using aromatic carboxylic acid anhydrides as dehydration condensation agents. In 1994, Prof. Isamu Shiina reported an acidic coupling method using Lewis acid, and, in 2002, a basic esterification using nucleophilic catalyst.
α,β-Unsaturated carbonyl compounds are organic compounds with the general structure (O=CR)−Cα=Cβ-R. Such compounds include enones and enals, but also carboxylic acids and the corresponding esters and amides. In these compounds, the carbonyl group is conjugated with an alkene. Unlike the case for carbonyls without a flanking alkene group, α,β-unsaturated carbonyl compounds are susceptible to attack by nucleophiles at the β-carbon. This pattern of reactivity is called vinylogous. Examples of unsaturated carbonyls are acrolein (propenal), mesityl oxide, acrylic acid, and maleic acid. Unsaturated carbonyls can be prepared in the laboratory in an aldol reaction and in the Perkin reaction.