Thermodynamics of the Lipase-Catalyzed Esterification of 1-Dodecanoic Acid with (−)-Menthol in Organic Solvents

The thermodynamics of the lipase-catalyzed stereospecific esterification of 1-dodecanoic acid with (−)-menthol in seven organic solvents have been investigated. Equilibrium measurements were performed using hexane, heptane, cyclohexane, toluene, 2,2,4-trimethylpentane, acetonitrile, and 2-methyl-2-butanol at the temperature T = 298.15 K. The equilibrium constants have been correlated with the (octanol + water) partition coefficients and the relative permittivities of the solvents. The saturation molalities and the (hexane + water) partition coefficients of (−)-menthol, 1-dodecanoic acid, and (−)-menthyl dodecanoate have also been determined at T = 298.15 K. The equilibrium constant of the esterification reaction in aqueous media has been calculated. An important finding is that the molality of water plays an important role in determining the extent of ester formation. In acetonitrile and 2-methyl-2-butanol, which have a very high molality of water, the formation of (−)-menthyl dodecanoate is considerably smaller. However, in hydrophobic solvents with lower molalities of water, the formation of (−)-menthyl dodecanoate is favored in the reaction mixture. The value of the equilibrium constant varies from 3 to 26. However, the molality of (−)-menthyl dodecanoate changes from 0.034 mmol kg-1 in acetonitrile to 16 mmol kg-1 in heptane. The change in product yield is a factor of ≈500 and is a striking example of the utility of organic solvents in biocatalysis.