Biphasic Reaction Engineering

The chemical equilibria of many industrially important organic reactions in aqueous solutions are often displaced in the direction of the reactants, leading to very low conversions. Therefore, there is a need for an environmentally friendly strategy that will shift the equilibria toward the products, resulting in enhanced conversions. A particularly effective technique is to add a second phase, appropriately termed biphasing. In general, biphasing is the intentional addition of an immiscible phase to a reaction mixture to increase the yield of the desired product or to facilitate separation of product from (say) catalyst. Much of the effort till recently has been on adding a water-immiscible organic solvent in enzyme-catalyzed organic reactions in the aqueous phase. Although strictly the term biphasing should apply only to soluble catalysts, thus preserving the purity of its definition, in practice it also includes insoluble catalysts such as immobilized enzymes (which would constitute a third phase). Biphasing received an exciting stimulus around 1984 when it was used to overcome the inherent and perhaps the most telling deficiency of homogeneous catalysis. By biphasing with an aqueous phase (unlike in enzymatic catalysis where the biphasing liquid is an organic solvent), the catalyst was fully retained in that phase, whereas the product (and unused reactant) remained in the organic phase. The consequent easy separation of catalyst from product added a new dimension to homogeneous catalysis that gives it a decided edge over its heterogeneous counterpart for many reactions. Yet another dimension to biphasing was added in the last decade when it was found that both phases could be aqueous. This variant of traditional biphasing has many obvious advantages. Although still in its infancy, its enormous potential is not difficult to visualize. The chief advantages and disadvantages of biphasing are listed in Table 18.1. We begin our treatment of biphasing by developing the theoretical foundation for predicting an apparent or effective equilibrium constant for a biphasic reaction. This will be done specifically for enzyme-catalyzed reactions, but it can be extended to straight organic synthesis. Several important aspects of these biphasic systems, such as solvent selection and the role of mass transfer, will be discussed.