Synthesis of a Macrocyclic Lactone. I. Reaction in Homogeneous Media

Abstract

Formation of a macrocyclic lactone, hexadecanolide, from the corresponding ω‐hydroxycarboxylic acid has been investigated using lipase as esterification catalyst. The parameters studied were water activity in the reaction medium, solvent polarity, type of lipase, and substrate concentration. Formation of non‐cyclic esters, i.e., intermolecular esterification, was found to compete with lactone formation and mixtures of both types of reaction products were obtained in all cases. It was also found that the reaction always yielded a mixture of oligomers of both cyclic and non‐cyclic nature. Under appropriate conditions (low water activity, nonpolar solvent) the starting ω‐hydroxycarboxylic acid was completely converted to ester products but the yield of the target product, the monomeric lactone, never exceeded 41%. All the reactions were carried out in organic solvents with small amounts of water present. A related investigation performed in microheterogeneous media consisting of water‐in‐oil microemulsions is reported separately.

Keywords:

• Lactone
• Hexadecanolide
• Synthesis
• Preparation
• Lipase
• Water activity
• Mass spectrometry

Acknowledgment

We are grateful to VINNOVA for economic support.