Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jun 13;14(13):9678-9686.
doi: 10.1021/acscatal.4c02028. eCollection 2024 Jul 5.

Deconvoluting Substrates, Support, and Temperature Effects on Leaching and Deactivation of Pd Catalysts: An In Situ Study in Flow

Oliver J Newton  1 , Matthew J Takle  1 , Jeffery Richardson  2 , Klaus Hellgardt  3 , King Kuok Mimi Hii  1
Affiliations

Deconvoluting Substrates, Support, and Temperature Effects on Leaching and Deactivation of Pd Catalysts: An In Situ Study in Flow

Oliver J Newton et al. ACS Catal. .

Abstract

Leaching behavior of three different Pd heterogeneous catalysts (PdEnCat 30, FibreCat FC1001, and Pd/Al2O3) during the Heck reaction of iodobenzene and methyl acrylate, in the presence of triethylamine, was compared using a tandem flow reactor. While leaching was observed in all three cases, Pd/Al2O3 appeared to be the most robust, showing little/no leaching at ambient temperature. The leached Pd species also appear to display different catalytic activities. With a slight modification of the reactor, the leaching caused by individual components of the reaction mixture can be assessed separately. For the polymer-supported catalysts, triethylamine caused the largest amount of leaching, even at 30 °C. In contrast, the leaching from Pd/Al2O3 was observed only in the presence of iodobenzene at 90 °C. Variations in leaching behavior were ascribed to differences in Pd species and immobilization methods.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Original configuration of the tandem flow reactor (configuration 1).
Scheme 1
Scheme 1. Heck Coupling between Iodobenzene and Methyl Acrylate to Form Methyl Cinnamate
Figure 2
Figure 2
Three heterogeneous Pd catalysts were selected for this study.
Figure 3
Figure 3
Reaction profiles of Heck coupling obtained using PdEnCat 30, FC-1001, and Pd/Al2O3 in toluene, dioxane, and DMF in batch reactors. Reaction conditions: Pd catalyst (1 mol %), PhI (3.84 mmol), methyl acrylate (7.40 mmol), NEt3 (7.40 mmol), solvent (50 mL), 90 °C. % Conversions to product were determined by HPLC (see S1.1, Supporting Information).
Figure 4
Figure 4
Evaluation of leaching of PdEnCat 30 in different solvents in the tandem flow reactor (configuration 1, Figure 1): (A) DMF (T1 = 90 °C, T2 = 110 °C); (B) DMF (T1 = 30 °C, T2 = 110 °C); (C) dioxane (T1 = 90 °C, T2 = 110 °C); and (D) toluene (T1 = 90 °C, T2 = 110 °C). Red = S1 conversions; blue = S2 conversions.
Figure 5
Figure 5
Assessing leaching of FC-1001 and Pd/Al2O3 at 90 °C (A and C, respectively) and 30 °C (B and D, respectively) in DMF, using a tandem reactor (configuration 1, Figure 1). T2 = 110 °C in all these experiments. Red = S1 conversions; blue = S2 conversions.
Figure 6
Figure 6
Modified tandem reactor (configuration 2) for monitoring leaching caused by individual reaction components.
Figure 7
Figure 7
Leaching experiments were conducted with PdEnCat30 using the modified reactor (configuration 2, Figure 6). Each experiment started with PBR (T1) at 30 °C (blue), then increased to 90 °C (red).
Scheme 2
Scheme 2. Reaction of Pd(OAc)2 with Triethylamine to Form Pd(0) via a Dehydrogenative Mechanism
Figure 8
Figure 8
Pd leaching from FC-1001 by PhI (A) and NEt3 (B). Each experiment started with PBR (T1) at 30 °C (blue), then increased to 90 °C (red).
Figure 9
Figure 9
Stability of Pd/Al2O3 in iodobenzene (A) and triethylamine (B). Each experiment started with PBR (T1) at 30 °C (blue), then increased to 90 °C (red).
See this image and copyright information in PMC

References

    1. Rayadurgam J.; Sana S.; Sasikumar M.; Gu Q. Palladium catalyzed C-C and C-N bond forming reactions: an update on the synthesis of pharmaceuticals from 2015–2020. Org. Chem. Front. 2021, 8 (2), 384–414. 10.1039/D0QO01146K. - DOI
    1. Devendar P.; Qu R.-Y.; Kang W.-M.; He B.; Yang G.-F. Palladium-Catalyzed Cross-Coupling Reactions: A Powerful Tool for the Synthesis of Agrochemicals. J. Agric. Food Chem. 2018, 66 (34), 8914–8934. 10.1021/acs.jafc.8b03792. - DOI - PubMed
    1. Hayler J. D.; Leahy D. K.; Simmons E. M. A Pharmaceutical Industry Perspective on Sustainable Metal Catalysis. Organometallics 2019, 38 (1), 36–46. 10.1021/acs.organomet.8b00566. - DOI
    1. Garrett C. E.; Prasad K. The Art of Meeting Palladium Specifications in Active Pharmaceutical Ingredients Produced by Pd-Catalyzed Reactions. Adv. Synth. Catal. 2004, 346 (8), 889–900. 10.1002/adsc.200404071. - DOI
    1. Vasquez-Cespedes S.; Betori R. C.; Cismesia M. A.; Kirsch J. K.; Yang Q. Heterogeneous Catalysis for Cross-Coupling Reactions: An Underutilized Powerful and Sustainable Tool in the Fine Chemical Industry?. Org. Process Res. Dev. 2021, 25 (4), 740–753. 10.1021/acs.oprd.1c00041. - DOI

LinkOut - more resources