Exploiting Phase Behavior for Coupling Homogeneous Reactions with Heterogeneous Separations in Sustainable Production of Pharmaceuticals

Abstract

John Prausnitz was never content to measure new data solely because the data were new. He always had an application in mind-a separation or even a process that required the data for implementation. We present here an advance in using designed changes in phase equilibria to enable the facile recovery and recycle of homogeneous catalysts. We show a new application of organic-aqueous tunable solvents (OATS) to run homogeneous reactions (fast rates and high selectivities) followed by facile and efficient heterogeneous separations and the recycle of the homogeneous catalysts. This is done by using CO 2 to manipulate the phase behavior of monophasic organic-water mixtures to form heterogeneous organic-rich and aqueous-rich phases. The example shown is the hydroformylation of hydrophobic p-methylstyrene catalyzed by rhodium catalyst to which is attached a hydrophilic phosphorus ligand. The OATS method increases the conversion rate of styrene to the aldehyde products by an order of magnitude compared to heterogeneously reported reactions. Also, the selectivity toward the branched aldehyde (the desired product) increases by 30 %. The hydrophobic product partitions into the organic-rich phase with more than 99 % removal efficiency, and the hydrophilic catalyst is retained in the aqueous-rich phase with 99.9 % efficiency. In addition, we recycle the catalyst for five consecutive reactions without significant loss of catalytic activity.

Reusable N-Heterocyclic Carbene Complex Catalysts and Beyond: A Perspective on Recycling Strategies

“…Complex 12 displayed the highest activity; a high yield of 98% with a 5 mol % loading was obtained after 3 h of reaction at room temperature. Complex 15 displayed a lower activity (76%) compared with that of complex 12, and we ascribed this discrepancy to the solubility difference of these two complexes, as the water solubility of the triethylamine-functionalized complex (12) is greater than that of the tributylamine-functionalized complex (15). The recyclability of ammonium-tagged SIPr-Cu(I) was validated; after the completion of reaction, ether was added to the reaction tube, the upper organic phase containing product was easily separated by simple liquid−liquid extractions to produce the final product triazole, and the residual aqueous catalyst phase was reused for the next run because of the obvious solubility difference between the ammonium salt functionalized [(SIPr)Cu X ] in ether and water.…”

“…Homogeneous recyclable catalysts and heterogenized (immobilized) homogeneous catalysts have been two main solutions considering both sides of activity and recycling (or separation). , Up to now, two main strategies, viz., (i) homogeneous catalysis and heterogeneous separationcatalysis under homogeneous conditions and separation in different phases − and (ii) immobilized (or heterogenized) homogeneous catalysts, have been extensively explored to recycle the catalysts. − These are two central themes that we will discuss in detail in this review.…”

Solvents for sustainable chemical processes

“…25) and p-methylstyrene (an analog for an ibuprofen precursor) were successfully conducted using OATS technology. 64,[81][82][83] The solubility of the 1-octene in water is less than 3 ppm. However, it is increased more than 10 000-fold by the addition of tetrahydrofuran (THF) as cosolvent.…”

Tunable solvents: Shades of green

“…A hydrophilic catalyst, for example an enzyme [43], or a homogeneous catalyst with modified hydrophilic ligands [44], is then separable and reusable. The product can then be isolated from the organic phase by conventional methods.…”