Lactonisation

Lactonisation is the intramolecular formation of a lactone. A lactone is a cyclic ester. This reaction typically occurs when a molecule contains both a hydroxyl group and a carboxylic acid group positioned such that they can react with each other to form a ring. The process involves the nucleophilic attack of the hydroxyl oxygen on the carbonyl carbon of the carboxylic acid, leading to the elimination of water and the creation of a cyclic ester.

The size of the lactone ring formed is a critical factor in the feasibility and rate of lactonisation. Small rings, such as three-membered or four-membered lactones, are generally unstable and difficult to form due to ring strain. Five-membered and six-membered lactones are typically the most thermodynamically stable and are readily formed. Larger rings can also be formed, but their formation may require specific conditions or catalysts due to entropic factors, as the molecule needs to adopt a specific conformation for cyclization to occur.

Lactonisation can be catalyzed by acids or bases. Acid catalysis typically involves the protonation of the carbonyl oxygen of the carboxylic acid, making the carbonyl carbon more electrophilic and susceptible to attack by the hydroxyl group. Base catalysis involves the deprotonation of the hydroxyl group, increasing its nucleophilicity. Various reagents and reaction conditions can be employed to facilitate lactonisation, depending on the specific substrate and desired outcome. This reaction is important in organic synthesis, particularly in the preparation of natural products and pharmaceuticals.