What is the best solvent combination for a catalytic biphasic reaction system to maximise equilibrium conversion? And which phase volume ratio and reaction stoichiometry maximises the conversion? Which product yield can be obtained using a distinct biphasic reaction mixture? These questions are essential, as optimisation can only be carried out within the thermodynamically imposed boundaries. Within this paper we introduce a mathematical expression to calculate and predict equilibrium conversion and product yield in biphasic reaction mixtures with only one reactive phase. This mathematical expression allows a time-saving design of biphasic experiments with respect to maximum conversion and product yield. The calculations were verified by experimental data obtained from a substrate-coupled alcohol dehydrogenase-catalysed reduction under different biphasic reaction conditions.

For the prediction and optimisation of the equilibrium conversion in biphasic catalysed reactions, the equilibrium constant of the desired reaction and the partition coefficients of all reactants have to be known. Within this contribution we have examined the alcohol dehydrogenase-catalysed reduction of several linear and aromatic ketones in biphasic reaction media with respect to equilibrium conversion. In this example, the equilibrium constant can be expressed in terms of differences in oxidation-reduction potentials DE 0 . However, for a large variety of organic compounds, these data are quite rare in the literature. To overcome this lack of data, we have utilised methods of computational chemistry to calculate data for the Gibbs free energy DG R leading to the equilibrium constants of a homologous series of linear ketones. To obtain comparable data for the reduction of substituted acetophenone derivatives, the Hammett relation leads to the necessary equilibrium constants. Furthermore, we compare the equilibrium conversions of a set of cofactor regeneration methods for the alcohol dehydrogenase-catalysed reductions. These results lead to a time-saving experimental design for the enantioselective reduction of 2-octanone to (R)-2-octanol on a preparative scale utilising biphasic reaction conditions.

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