lactone

β-propiolactone, formed from β-hydroxypropionic acid

In chemistry, a lactone is a cyclic ester ^[1] which can be seen as the condensation product of an alcohol group -OH and a carboxylic acid group -COOH in the same molecule. It is characterized by a closed ring consisting of two or more carbon atoms and a single oxygen atom, with a ketone group =O in one of the carbons adjacent to the latter.

Nomenclature

Lactone nomenclature: α-acetolactone, β-propiolactone, γ-butyrolactone, and δ-valerolactone

Lactones are usually named according to the precursor acid molecule (aceto = 2 carbons, propio = 3, butyro = 4, valero = 5, capro = 6, etc.), with a -lactone suffix and a Greek letter prefix that specifies the number of carbons in the heterocyle — 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, etc..

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). An internal dehydration within the same molecule of lactic acid would have produced alpha-propiolactone, an unstable^{[citation needed]} lactone with a 3-membered ring.

Natural sources

Lactones (specifically 3-methyl-4-octanolide) are found in oak trees as well as many other plants, and impart flavour to whisky.

Synthesis

Many methods in ester synthesis can also be applied to that of lactones. In one industrial synthesis of oxandrolone the key lactone-forming step is an organic reduction - esterification ^{[2] [3]}:

In halolactonization, an alkene is attacked by a halogen via electrophilic addition with the cationic intermediate captured intramolecularly by an adjacent carboxylic acid (See also iodolactamization), for example in this iodolactonization ^[4]:

A specific method is called Yamaguchi esterification.

A recent study has isolated β-lactones from bromination of 2,3-dimethylmaleate and/or 2,3-dimethylfumarate disodium salts, under ambient and aqueous conditions. The carboxylate groups of the maleate and fumarate moieties exhibit neighbouring group effects and alpha-lactones are proposed in the detailed mechanism.

Reactions

The most stable structure for lactones are the 5-membered lactones (gamma-lactone) and 6-membered lactones (delta-lactone), because of the minimal angle strain in the compounds' structure. Gamma-lactones are so stable that, in the presence of dilute acids at room temperature, 4-hydroxy acids (R-CH(OH)-(CH₂)₂-COOH) immediately undergo spontaneous esterification and cyclisation to the lactone. Beta-lactones do exist, but can only be made by special methods. Alpha-lactones can be detected as transient species in mass spectrometry experiments.^[5]

The reactions of lactones are similar to those of esters, as exemplified by gamma-lactone in the following sections:

Hydrolysis

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 higher than that of the straight-chained ester i.e. the products (hydroxyacids) are favoured 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.

Reduction

Lactones can be reduced to diols using lithium aluminium hydride in dry ether. The reduction reaction will first break the ester bond of the lactone and then, reduce the carboxylic acid group (-COOH) to the alcohol group (-OH). Gamma-lactones, for instance, will be reduced to butane-1,4-diol, (CH₂(OH)-(CH₂)₂-CH₂(OH)

Aminolysis

Lactones also react with ethanolic ammonia, which will first break the ester bond and then react with the acidic -COOH group, because of the basic properties of ammonia, to form a difunctional group, i.e. alcohol and amide. Gamma-lactones will react to yield CH₂(OH)-(CH₂)₂-CO-NH₂.

Michael reaction

Sesquiterpene lactones, found in many plants, can react with other molecules via a Michael reaction.

Examples

β-propiolactone

γ-butyrolactone (GBL)

D-glucono-δ-lactone (E575)

ε-caprolactone

See also

• Lactam, a cyclic amide
• Lactim, a cyclic imide

References & notes