Lactones are cyclic

carboxylic ester In chemistry, an ester is a chemical compound, 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 c ...

s. They are derived from the corresponding hydroxycarboxylic acids by

esterification 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 ...

. They can be saturated or unsaturated. Lactones are formed by lactonization, the intramolecular esterification of the corresponding hydroxycarboxylic acids.

Nomenclature

Greek prefixes in alphabetical order indicate ring size. 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 Macrocycles are often described as molecules and ions containing a ring of twelve or more atoms. Classical examples include the crown ethers, calixarenes, porphyrins, and cyclodextrins. Macrocycles describe a large, mature area of chemistry. ...

lactones are known as macrolactones. The other suffix used to denote a lactone is ''-olide'', used in substance class names like ''

butenolide Butenolides are a class of lactones with a four-carbon heterocycle, heterocyclic ring structure.Joule JA, Mills K. (2000). Heterocyclic Chemistry 4th ed. Blackwell Science Publishing: Oxford, UK They are sometimes considered redox, oxidized deri ...

'', ''

macrolide Macrolides are a class of mostly natural products with a large macrocyclic lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, may be attached. Macrolides belong to the polyketide class of natural products. ...

'', ''

cardenolide A cardenolide is a type of steroid. Many plants contain derivatives, collectively known as cardenolides, including many in the form of cardenolide glycosides (cardenolides that contain structural groups derived from sugars). Cardenolide glycoside ...

'' or ''

bufadienolide Bufadienolide is a chemical compound with steroid structure. Its derivatives are collectively known as bufadienolides, including many in the form of bufadienolide glycosides (bufadienolides that contain structural groups derived from sugars). These ...

''. To obtain the

preferred IUPAC name In chemical nomenclature, a preferred IUPAC name (PIN) is a unique name, assigned to a chemical substance and preferred among all possible names generated by IUPAC nomenclature. The "preferred IUPAC nomenclature" provides a set of rules for choo ...

s, 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.

Etymology

The name ''lactone'' derives from the ring compound called

lactide Lactide is the lactone cyclic ester derived by multiple esterification between two (usually) or more molecules from lactic acid (2-hydroxypropionic acid) or other hydroxy carboxylic acid. They are designated as dilactides, trilactides, etc., acc ...

, which is formed from the dehydration of 2-hydroxypropanoic acid (

lactic acid Lactic acid is an organic acid. It has the molecular formula C3H6O3. It is white in the solid state and it is miscible with water. When in the dissolved state, it forms a colorless solution. Production includes both artificial synthesis as wel ...

) 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 Théophile-Jules Pelouze (also known as Jules Pelouze), ; 26 February 180731 May 1867) was a French chemist. Life He was born at Valognes, and died in Paris. His father, Edmond Pelouze, was an industrial chemist and the author of several tech ...

, who first obtained it as a derivative of lactic acid. An internal

dehydration reaction In chemistry, a dehydration reaction is a chemical reaction that involves the loss of an H2O from the reacting molecule(s) or ion(s). This reaction results in the release of the H2O as water. When the reaction involves the coupling of two molecu ...

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 Wilhelm Rudolph Fittig (6 December 183519 November 1910) was a German chemist. He discovered the pinacol coupling reaction, mesitylene, diacetyl and biphenyl. Fittig studied the action of sodium on ketones and hydrocarbons. He discovered the Fi ...

extended the name "lactone" to all intramolecular carboxylic esters.

Occurrence

Lactone rings occur widely as building blocks in nature, such as in

ascorbic acid Ascorbic acid is an organic compound with formula , originally called hexuronic acid. It is a white solid, but impure samples can appear yellowish. It dissolves freely in water to give mildly acidic solutions. It is a mild reducing agent. Asco ...

, kavain,

nepetalactone Nepetalactone is a name for multiple iridoid Structural analog, analog stereoisomers. Nepetalactones are produced by ''Nepeta cataria'' (catnip) and many other plants belonging to the genus ''Nepeta'', in which they protect these plants from herbiv ...

, gluconolactone,

hormones A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physiology and behavior. Hormones a ...

(

spironolactone Spironolactone, sold under the brand name Aldactone among others, is classed as a diuretic medication. It can be used to treat edema, fluid build-up due to hepatic cirrhosis, liver disease or kidney disease. It is also used to reduce risk o ...

, mevalonolactone),

enzymes An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as pro ...

(

lactonase Lactonase (EC 3.1.1.81, acyl-homoserine lactonase; systematic name ''N''-acyl-L-homoserine-lactone lactonohydrolase) is a metalloenzyme, produced by certain species of bacteria, which targets and inactivates acylated homoserine lactones (AHLs). ...

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...

s ( butyrolactone,

avermectin The avermectins are a group of 16-membered Macrolide, macrocyclic lactone derivatives with potent anthelmintic and Insecticide, insecticidal properties. These naturally occurring compounds are generated as fermentation products by ''Streptomyces a ...

s),

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...

s (

s like

erythromycin Erythromycin is an antibiotic used for the treatment of a number of bacterial infections. This includes respiratory tract infections, skin infections, chlamydia infections, pelvic inflammatory disease, and syphilis. It may also be used ...

;

amphotericin B Amphotericin B is an antifungal medication used for serious fungal infections and leishmaniasis. The fungal infections it is used to treat include mucormycosis, aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, and cryptococ ...

), anticancer drugs ( vernolepin, epothilones),

phytoestrogen A phytoestrogen is a plant-derived xenoestrogen (a type of estrogen produced by organisms other than humans) not generated within the endocrine system, but consumed by eating plants or manufactured foods. Also called a "dietary estrogen", it ...

s ( resorcylic acid lactones,

cardiac glycoside Cardiac glycosides are a class of organic compounds that increase the output force of the heart and decrease its rate of contractions by inhibiting the cellular sodium-potassium ATPase pump. Their beneficial medical uses include treatments for ...

s). 5-Membered γ-lactones and 6-membered δ-lactones are prevalent. β-lactones appear in a number of natural products. αLactones can be detected as transient species in

mass spectrometry Mass spectrometry (MS) is an analytical technique that is used to measure the mass-to-charge ratio of ions. The results are presented as a ''mass spectrum'', a plot of intensity as a function of the mass-to-charge ratio. Mass spectrometry is used ...

experiments. Macrocyclic lactones are also important natural products. Lactones are present in

oak An oak is a hardwood tree or shrub in the genus ''Quercus'' of the beech family. They have spirally arranged leaves, often with lobed edges, and a nut called an acorn, borne within a cup. The genus is widely distributed in the Northern Hemisp ...

wood, and they contribute to the flavour profile of

barrel-aged beer A barrel-aged beer is a beer that has been aged for a period of time in a wooden barrel. Typically, these barrels once housed bourbon, whisky, wine, or, to a lesser extent, brandy, sherry, or port. Many methods in ester synthesis can also be applied to that of lactones. Lactonization competes with

polymerization In polymer chemistry, polymerization (American English), or polymerisation (British English), is a process of reacting monomer molecules together in a chemical reaction to form polymer chains or three-dimensional networks. There are many fo ...

for longer hydroxy acids, or the strained βlactones. γLactones, on the other hand, are so stable that 4-hydroxy acids (R-CH(OH)-(CH₂)₂-CO₂H) spontaneously cyclize. In one industrial synthesis of

oxandrolone Oxandrolone is an androgen and synthetic anabolic steroid (AAS) medication to help promote weight gain in various situations, to help offset protein catabolism caused by long-term corticosteroid therapy, to support recovery from severe burns, t ...

the key lactone-forming step is an

organic reaction Organic reactions are chemical reactions involving organic compounds. The basic organic chemistry reaction types are addition reactions, elimination reactions, substitution reactions, pericyclic reactions, rearrangement reactions, mechanistic organ ...

– esterification. Iodolactonization

In halolactonization, 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 ...

is attacked by a

halogen The halogens () are a group in the periodic table consisting of six chemically related elements: fluorine (F), chlorine (Cl), bromine (Br), iodine (I), and the radioactive elements astatine (At) and tennessine (Ts), though some authors would ...

via

electrophilic addition In organic chemistry, an electrophilic addition (AE) reaction is an addition reaction where a chemical compound containing a double or triple bond has a π bond broken, with the formation of two new σ bonds.March, Jerry; (1985). Advanced Organic ...

with the cationic intermediate captured intramolecularly by an adjacent

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 ...

. Specific methods include Yamaguchi esterification, Shiina macrolactonization, Corey-Nicolaou macrolactonization,

Baeyer–Villiger oxidation The Baeyer–Villiger oxidation is an organic reaction that forms an ester from a ketone or a lactone from a cyclic ketone, using peroxyacids or peroxides as the oxidant. The reaction is named after Adolf von Baeyer and Victor Villiger who first ...

and

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 ...

. An alternative radical reaction yielding γ-lactones is the manganese-mediated coupling.

Reactions

Lactones exhibit the reactions characteristic of esters.

Hydrolysis and aminolysis

Heating a lactone with a base (

sodium hydroxide Sodium hydroxide, also known as lye and caustic soda, is an inorganic compound with the formula . It is a white solid ionic compound consisting of sodium cations and hydroxide anions . Sodium hydroxide is a highly corrosive base (chemistry), ...

) will

hydrolyse 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 ...

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 A reversible reaction is a reaction in which the conversion of reactants to products and the conversion of products to reactants occur simultaneously. : \mathit aA + \mathit bB \mathit cC + \mathit dD A and B can react to form C and D or, in the ...

, with an

equilibrium Equilibrium may refer to: Film and television * ''Equilibrium'' (film), a 2002 science fiction film * '' The Story of Three Loves'', also known as ''Equilibrium'', a 1953 romantic anthology film * "Equilibrium" (''seaQuest 2032'') * ''Equilibr ...

. However, the

equilibrium constant The equilibrium constant of a chemical reaction is the value of its reaction quotient at chemical equilibrium, a state approached by a dynamic chemical system after sufficient time has elapsed at which its composition has no measurable tendency ...

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 Entropy is a scientific concept, most commonly associated with states of disorder, randomness, or uncertainty. The term and the concept are used in diverse fields, from classical thermodynamics, where it was first recognized, to the micros ...

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.

Reduction

Lactones can be reduced to diols using

lithium aluminium hydride Lithium aluminium hydride, commonly abbreviated to LAH, is an inorganic compound with the chemical formula or . It is a white solid, discovered by Finholt, Bond and Schlesinger in 1947. This compound is used as a reducing agent in organic synthe ...

. For instance, gamma-lactones is reduced to butane-1,4-diol, (CH₂(OH)-(CH₂)₂-CH₂(OH).

Polymerization

Some lactones convert to polyesters: For example the double lactone called

polymerizes to

polylactic acid Polylactic acid, also known as poly(lactic acid) or polylactide (PLA), is a plastic material. As a thermoplastic polyester (or polyhydroxyalkanoate) it has the backbone formula or . PLA is formally obtained by condensation of lactic acid with ...

(polylactide). The resulting polylactic acid has been heavily investigated for commercial applications. : Polylactide_synthesis_v

Uses

Flavors and fragrances

Lactones contribute significantly to the flavor of fruit, and of unfermented and fermented dairy products, and are therefore used as flavors and fragrances. Some examples are

γ-decalactone γ-Decalactone is a lactone and aroma compound with the chemical formula C10H18O2. It has an intense peach taste, flavour, naturally present in many fruits and fermentations. It is particularly important in the formulation of peach, apricot, and ...

(4-decanolide), which has a characteristic peach flavor;

δ-decalactone δ-Decalactone (DDL) is a chemical compound, classified as a lactone, that naturally occurs in fruit and milk products in traces. It can be obtained from both chemical and biological sources. Chemically, it is produced from Baeyer–Villiger oxid ...

(5-decanolide), which has a creamy coconut/peach flavour; γ-dodecalactone (4-dodecanolide), which also has a coconut/fruity flavor, a description which also fits γ-octalactone (4-octanolide), although it also has a herbaceous character; γ-nonalactone, which has an intense coconut flavor of this series, despite not occurring in coconut, and γ-undecalactone. Macrocyclic lactones ( cyclopentadecanolide, 15-pentadec-11/12-enolide) have odors similar to macrocyclic ketones of animal origin (

muscone Muscone is a macrocycle, macrocyclic ketone, an organic compound that is the primary contributor to the odor of deer musk. Natural muscone is obtained from musk, a glandular secretion of the musk deer, which has been used in perfumery and medicin ...

civetone Civetone is a macrocyclic ketone and the main odorous constituent of civet oil. It is a pheromone sourced from the African civet. It has a strong musky odor that becomes pleasant at extreme dilutions. Civetone is closely related to muscone, the ...

Plastics

Polycaprolactone Polycaprolactone (PCL) is a synthetic, semi-crystalline, biodegradable polyester with a melting point of about 60 °C and a glass transition temperature of about −60 °C. The most common use of polycaprolactone is in the production ...

is an important plastic. Its formation has even been considered in the context of the

origin of life Abiogenesis is the natural process by which life arises from abiotic component, non-living matter, such as simple organic compounds. The prevailing scientific hypothesis is that the transition from non-living to organism, living entities on ...

Dilactones

Ellagic acid Ellagic acid is a polyphenol found in numerous fruits and vegetables. It is the dilactone of hexahydroxydiphenic acid. Name The name comes from the French term ''acide ellagique'', from the word ''galle'' spelled backward because it can be o ...

(Hexahydroxydiphenic acid dilactone) *

Flavogallonic acid dilactone Flavogallonic acid dilactone is a hydrolysable tannin that can be found in '' Rhynchosia volubilis'' seeds, in '' Shorea laevifolia'', in ''Anogeissus leiocarpus'' and ''Terminalia avicennoides ''Terminalia avicennioides'' () is a tree species ...

can be found in '' Rhynchosia volubilis'' seeds and in ''Shorea laeviforia'' *

Lactide Lactide is the lactone cyclic ester derived by multiple esterification between two (usually) or more molecules from lactic acid (2-hydroxypropionic acid) or other hydroxy carboxylic acid. They are designated as dilactides, trilactides, etc., acc ...

* Tergallic acid dilactone can be found in ''Rhynchosia volubilis'' seeds *

Valoneic acid dilactone Valoneic acid dilactone is a hydrolysable tannin that can be isolated from the heartwood of '' Shorea laevifolia''5A-Reductase inhibitory tannin-related compounds isolated from Shorea laevifolia. Yoshio Hirano, Ryuichiro Kondo and Kokki Sakai, Jou ...

can be isolated from the heartwood of ''Shorea laeviforia'' * Ethylene brassylate (Musk T), a widely used synthetic musk

References and notes

{{Authority control Functional groups