Lactones are cycliccarboxylic esters. They are derived from the correspondinghydroxycarboxylic acids byesterification. They can be saturated or unsaturated.[1]
Lactones are formed bylactonization, the intramolecular esterification of the corresponding hydroxycarboxylic acids.[2]
Greek prefixes in alphabetical order indicate ring size.
| Ring size (number of atoms in the ring) | Systematic name | IUPAC name | Parent lactone | Structure, comment |
|---|---|---|---|---|
| 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 asmacrolactones.[3]
The other suffix used to denote a lactone is-olide, used in substance class names likebutenolide,macrolide,cardenolide orbufadienolide.
To obtain thepreferred 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 namelactone derives from the ring compound calledlactide, 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 chemistThéophile-Jules Pelouze, who first obtained it as a derivative of lactic acid.[5] An internaldehydration reaction within the same molecule of lactic acid would have producedalpha-propiolactone, a lactone with a 3-membered ring.
In 1880 the German chemistWilhelm Rudolph Fittig extended the name "lactone" to all intramolecular carboxylic esters.[6]
Lactone rings occur widely as building blocks in nature, such as inascorbic acid,kavain,nepetalactone,gluconolactone,hormones (spironolactone,mevalonolactone),enzymes (lactonase),neurotransmitters (butyrolactone,avermectins),antibiotics (macrolides likeerythromycin;amphotericin B),anticancer drugs (vernolepin,epothilones),phytoestrogens (resorcylic acid lactones,cardiac glycosides).
5-Membered γ-lactones and 6-membered δ-lactones are prevalent. β-lactones appear in a number of natural products.[7] α‑Lactones can be detected as transient species inmass spectrometry experiments.[8]
Macrocyclic lactones are also important natural products.[9] Lactones are present inoak wood, and they contribute to the flavour profile ofbarrel-aged beers.[10]
Many methods in ester synthesis can also be applied to that of lactones. Lactonization competes withpolymerization 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 cyclize.
In one industrial synthesis ofoxandrolone the key lactone-forming step is anorganic reaction – esterification.[11][12]
Inhalolactonization, analkene is attacked by ahalogen viaelectrophilic addition with the cationic intermediate captured intramolecularly by an adjacentcarboxylic acid.[13]
Specific methods includeYamaguchi esterification,Shiina macrolactonization,Corey-Nicolaou macrolactonization,Baeyer–Villiger oxidation andnucleophilic abstraction.
An alternative radical reaction yielding γ-lactones is themanganese-mediated coupling.
Lactones exhibit the reactions characteristic of esters.
Heating a lactone with a base (sodium hydroxide) willhydrolyse the lactone to its parent compound, the straight chained bifunctional compound. Like straight-chained esters, the hydrolysis-condensation reaction of lactones is areversible reaction, with anequilibrium. However, theequilibrium 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 theenthalpies of the hydrolysis of esters and lactones are about the same, theentropy 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 usinglithium aluminium hydride. For instance, gamma-lactones is reduced to butane-1,4-diol, (CH2(OH)-(CH2)2-CH2(OH).
Some lactones convert to polyesters:[14][15] For example the double lactone calledlactide polymerizes topolylactic acid (polylactide). The resulting polylactic acid has been heavily investigated for commercial applications.[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 areγ-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 fitsγ-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] andγ-undecalactone.
Macrocyclic lactones (cyclopentadecanolide,15-pentadec-11/12-enolide) have odors similar to macrocyclic ketones of animal origin (muscone,civetone).[9]
Polycaprolactone is an important plastic. Its formation has even been considered in the context of theorigin of life.[21]
