Know your enemy: aiding palladium extraction with a breath of fresh air Marina Economidou, Nisha Mistry, Katherine Wheelhouse, David Lindsay GSK/University of Strathclyde, UK Palladium-catalysed reactions find great utility in the pharmaceutical industry, as they offer a facile way of accessing important functional motifs in molecules through the formation of carbon‑carbon or carbon-heteroatom bonds. 1 Paralleling the increased use of catalysts in synthesis, however, is the demand for efficient methods of palladium recovery. With industry reports on the inconsistent removal of palladium following catalytic synthetic steps on manufacturing scale, there seems to be a knowledge gap as to which factors affect the efficiency of extraction and why there can be significant differences between laboratory and plant conditions. 2 We began with initial scoping experiments with N -acetyl cysteine to investigate the partition of palladium catalysts between the organic and aqueous phases. It was observed that only two of the seven phosphine ligands investigated were able to form PdL( N ‑acetylcysteine) complexes, demonstrating that there is a dependence of the extraction on the nature of the phosphine, likely related to the ligand cone angle. Subsequent experiments with bidentate phosphine ligands on a model aminocarbonylation reaction proved that palladium removal can be improved by over 32% on exposure of the organic phase to air, relative to an inert non‑isolated chemical environment. The performance of an array of functionalised silicas was also examined. Interestingly, extraction efficiency was unaffected by the inertness of the conditions, potentially indicating that the physical state of the extractant may be influencing the metal removal process. Extraction experiments on Pd 0 and Pd 2+ catalysts demonstrated that Pd 2+ extraction is equally efficient under both inert and non-inert conditions. Pd 0 catalysts, however, remained in the organic phase when treated in the glovebox, whereas almost complete removal was observed in air. To deconvolute whether the differential extraction efficacy is dependent on the physical state of the extractant, future work includes screening liquid scavengers. A wide array of chemical functionalities will be selected, with the major ones reported in literature being dithiocarbamates, xanthates and thiols. 3 Although oxidation state is considered to be the major cause of the difference in extraction efficiency, it is speculated that steric bulk may also have an impact. To investigate whether steric bulk influences extraction, future aims include scavenging of catalysts containing phosphines with a range of Tolman cone angles. 4 References 1. D. Basu, S. Achanta, N. U. Kumar, R. B. Rehani and R. Bandichhor, in Organometallics in Process Chemistry , eds. T. J. Colacot and V. Sivakumar, Springer Nature AG, Switzerland, 2019, pp. 115-160. 2. K. K nigsberger, G. P. Chen, R. R. Wu, M. J. Girgis, K. Prasad, O. Repi and T. J. Blacklock, Org. Process Res. Dev. , 2003, 7 , 733-742. 3. C. E. Garrett and K. Prasad, Adv. Synth. Catal. , 2004, 346, 889-900. 4. C. A. Tolma, J. Am. Chem. Soc. , 1970, 92 , 2956-2965.
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