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]
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 lactones are known as macrolactones.[3]
Look up macrolactone in Wiktionary, the free dictionary.
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]
Etymology
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 cannot be isolated but can only be made by special methods. α-lactones can be detected as transient species in mass spectrometry experiments.[7] 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.
Many methods in ester synthesis can also be applied to that of lactones. Lactonization competes with polymerization for longer hydroxy acids. γ-Lactones, on the other hand, are so stable that 4-hydroxy acids (R-CH(OH)-(CH2)2-CO2H) spontaneously cyclise to the lactone.
Lactones exhibit the reactions characteristic of esters.
Hydrolysis and ammonlysis
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 to give the ring-opend alcohol and amide.
Reduction
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).
Polymerization
Lactones readily form polyesters according to the formula, and have been shown to oligomerize without catalyst as well:[13][14]
Lactones contribute significantly to the flavor of fruit, and of unfermented and fermented dairy products,[17] and are therefore used as flavors and fragrances.[8] Some examples are γ-decalactone (4-decanolide), which has a characteristic peach flavor;[17]δ-decalactone (5-decanolide), which has a creamy coconut/peach flavour; γ-dodecalactone (4-dodecanolide), which also has a coconut/fruity flavor,[17] a description which also fits γ-octalactone (4-octanolide),[18] although it also has a herbaceous character;[17]γ-nonalactone, which has an intense coconut flavor of this series, despite not occurring in coconut,[19] 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).[8]
Prebiotic chemistry
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.[20]
^Pelouze, J. (9 December 1844). "Mémoire sur l'acide lactique" [Memoir on lactic acid]. Comptes rendus (in French). 19: 1219–1227.
From p. 1223: "Indépendamment de la lactide dont je viens de rappeler l'existence dans les produits de la distllation de l'acide lactique, celui-ci donne encore, par sa décomposition, une autre substance, que je propose d'appeler lactone, parce qu'elle me paraît être à l'acide lactique ce que l'acétone est à l'acide acétique." (Independently of the lactide of which I have just recalled the existence in the products of the distillation of lactic acid, this [i.e., lactic acid] gives further, by its decomposition, another substance, which I propose to call lactone, because it seems to me to be to lactic acid what acetone is to acetic acid.)
Reprinted: Pelouze, J. (1845). "Mémoire sur l'acide lactique" [Memoir on lactic acid]. Annales de Chimie et de Physique. 3rd series (in French). 13: 257–268. ; see p. 262.
English translation: Pelouze, J. (January 15, 1845). "Researches on lactic acid". The Chemical Gazette. 3 (54): 29–35. ; see p. 31.
^Fittig, Rudolph (1880). "Untersuchungen über ungesättige Säuren, dritte Abhandlung" [Investigations into unsaturated acids, third article]. Annalen der Chemie und Pharmacie (in German). 200: 1–96. doi:10.1002/jlac.18802000102. From p. 62: "Es ist wünschenswerth, für diese Gruppe von Verbindungen, deren bis jetzt einfachster Repräsentant der im Vorstehenden beschriebene Körper ist, eine allgemeine Bezeichnungsweise zu haben, und da der Name "Lactide" nicht anwendbar ist, weil dann das Lactid κατ εξοχην kein Lactid sein wurde, so schlagen wir als Gruppenbezeichnung den Namen "Lactone" vor". (It's desirable for this group of compounds — whose simplest representative until now has been the substance that's described in the preceding — to have a general designation, and since the name "lactide" isn't applicable because then the archetypal lactide would not be a lactide, we therefore suggest the name "lactone" as the designation of this group [of compounds].)
^Detlef Schröder, Norman Goldberg, Waltraud Zummack, Helmut Schwarz, John C. Poutsma and Robert R. Squires (1997), Generation of α-acetolactone and the acetoxyl diradical •CH2COO• in the gas phase. International Journal of Mass Spectrometry and Ion Processes, Volumes 165-166, November issue, Pages 71-82. doi:10.1016/S0168-1176(97)00150-X
^Development of a Commercial Process to Produce Oxandrolone John E. Cabaj, David Kairys, and Thomas R. Benson Org. Process Res. Dev.; 2007; 11(3) pp 378–388; (Article) doi:10.1021/op060231b
^R. Auras; L.-T. Lim; S. E. M. Selke; H. Tsuji (2010). Poly(lactic acid): Synthesis, Structures, Properties, Processing, and Applications. Wiley. ISBN978-0-470-29366-9.
