LACTONE

In chemistry, a lactone is a cyclic ester 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 other oxygen.

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

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]

Specific methods include Yamaguchi esterification and nucleophilic abstraction.

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 γ-lactones and 6-membered δ-lactones because, as in all organic cycles, 5 and 6 membered rings minimize the strain of bond angles. γ-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. β-lactones do exist, but can only be made by special methods. α-lactones can be detected as transient species in mass spectrometry experiments.^[6]

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 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 give only a single product.

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). For instance, gamma-lactones will be reduced to butan-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.

http://en.wikipedia.org/wiki/Lactone

Examples

Artemisinin, a new, highly-effective anti-malarial compound, is a sesquiterpene lactone found in Chinese wormwood. Lactucin, desoxylactucin, lactucopicrin, lactucin-15-oxalate, lactucopicrin-15-oxalate are some of the most prominent found in lettuce and spinach, giving most of the bitter taste to these crops.

One eudesmanolide, 3-oxo-5αH,8βH-eudesma-1,4(15),7(11)-trien-8,12-olide, can work with vernolic acid and other compounds in plants to reduce inflammation

http://en.wikipedia.org/wiki/Sesquiterpene_lactone

 

Synthesis of lactones and related compounds

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