Lactone



A lactone is a cyclic molecule. 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.

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 a 3-membered lactone which is unstable.

Nomenclature

Lactones are named by labelling the carbon atoms in the chain of the lactones' precursor compounds. The first carbon atom after the carbon in the -COOH group on the parent compound is labelled alpha, the second will be labelled beta and so forth. The lactone formed will be named after the carbon atom which is connected to the -OH (hydroxy) group that the -COOH group reacts with, and this will determine the prefix of the lactone. The prefixes also indicate the ring size: beta-lactone (4-membered), gamma-lactone (5-membered), delta-lactone (6-membered ring).


Synthesis

Many methods in esterification [2] [3]:

In halolactonization, an carboxylic acid (See also iodolactamization), for example in this iodolactonization [4]:

Reactions

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 (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)

Ammonolysis

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.

Examples

See also


References & notes

  1. ^ March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure Michael B. Smith, Jerry March Wiley-Interscience, 5th edition, 2001, ISBN 0-471-58589-0
  2. ^ 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
  3. ^ The complete reaction sequence is bromination to a sodium borohydride and intramolecular lactone formation
  4. ^ Organic Syntheses, Coll. Vol. 7, p.164 (1990); Vol. 64, p.175 (1986) Article link.
 
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