Coupling Homogeneous Reactions with Heterogeneous Separations Toward Sustainable Production of Pharmaceuticals

Designing changes in phase equilibria enables the facile and efficient recovery of homogeneous catalysts and their subsequent recycle.  Organic-Aqueous Tunable Solvents (OATS) can be used to couple homogeneous reactions (fast rates and high selectivity) with heterogeneous separations. Upon reaction completion, the separation is simply conducted by applying CO₂ pressure to manipulate the phase behavior of the initial monophasic organic−water mixtures. As a result, a phase split can be induced resulting in two phases:  one organic-rich and one aqueous-rich phase.  The products are separated at this stage (organic-rich phase) from the catalysts-containing phase which can now be recycled. Several examples will be presented and discussed, including the Rhodium-catalyzed hydroformylation of model compounds applicable to the synthesis of ibuprofen.  We will demonstrate that very modest CO₂ pressures (around 3 MPa) enable the recovery of up to 99% of the product and 99.9 % of the relatively hydrophobic catalyst. The presentation will be aimed at demonstrating the breath of OATS technology to develop alternative strategies toward the sustainable production of pharmaceuticals.