Can Palladium do what the Rhodium-workhorse cannot do? A case of scalable Isoselective hydroformylation

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By: Valentinos Mouarrawis and Sander Kluwer

The importance of hydroformylation cannot be overstated! This chemical reaction entails the addition of syngas, a mixture of carbon monoxide (CO) and hydrogen (H2), to olefins in the presence of a catalyst to produce aldehydes. Since its discovery by Otto Roelen in 1938, the hydroformylation process has evolved into one of the largest homogeneous catalyzed reactions applied in industry. To illustrate the vast size on which the technology is applied, hydroformylation produces nearly 14 million metric tons a year of products with a value of about € 15 billion euros. The resulting aldehydes are valuable compounds and find application in the production of detergents, fragrances, specialty polymers, and pharmaceutical active ingredients (APIs) but can also be further converted to the corresponding alcohols, carboxylic acids, amines, etc.  

In this blog, we highlight the work published by the Dydio research group in Angewandte Chemie ( demonstrating an industrially relevant method for the synthesis of isobutyrladehyde. The hydroformylation of propylene is an important application in the chemical industry, producing annually over 7 million tons of n-butyraldehyde and isobutyraldehyde mixture. The growing demand for isobutyraldehyde has been sparked by the use as starting material for the production of plasticizers, coatings, solvents, cleaners, food additives, etc. With the increased demand of the isoaldehyde, also the demand for more isoselective catalysts has emerged. However, the current industrial methods utilizing rhodium catalysts have been developed over the years toward the n-selective (linear) production of n-butyraldehyde. The progress made towards branched selectivity is largely academic using heterobidentate (BOB-Phos) ligands or sophisticated supramolecular “encapsulated” catalysts that were developed at the Reek Research group in Amsterdam. In a collaboration between the Reek group and Eastman Company, the latter type of catalysts have been developed further to make the systems applicable under industrially relevant conditions, demonstrating high activity and unrivaled selectivity for 1-octene hydroformylation.

Palladium is often called the chameleon of catalysis due to its versatile chemistry. Although commonly not taken in the list of metals that have been successfully applied in hydroformylation (Rh, Co, Ru), palladium has been investigated for this reaction. Particularly, the work of Eite Drent in the 80’s and 90’s of last millennium has shown that chemistry can be nicely tuned with high precision between hydroformylation (RC(O)H)), hydroacylation (RC(O)R), and polyketone (RC(O)R[C(O)R]n) formation of which one of the authors of this blog was involved. The details of these reactions mostly emerged in patent literature. Key to stirring the chemoselectivity is the judicious choice of electron-rich phosphorus ligands and anion. The bidentate ligands of most interest are still not commonly found in catalysis literature showing that this technology has not been taken up by the academic field.

In the new contribution, Dydio and coworkers have developed a palladium-based catalyst employing simple monodentate ligands, making the technology available for large-scale use. One crucial finding is that the authors discovered that iodide can act as an active ligand, working with phosphines to form the aldehyde products. They selected the industrially relevant propene as substrate which is also the most challenging substrate for obtaining isoselectivity. To this end, they screened an extensive and diverse ligand library and correlated descriptive Tolman and cone angle parameters to the activity (TOF) and selectivity (iso/n ratio) of the catalyst. The chemical space was explored using phosphine ligands, various reaction temperatures, PdX2 precursors, amounts of I2 or iodide, ligand/Pd ratios, and CO/H2 ratios and led to a catalytic system with iso/n selectivity ranging from 2:1 to 50:1 (120-80 °C). The use of PdI2, tricyclohexylphoshine, and anisole as the solvent make this process industry-friendly that can be potentially applied in commercial scale.

As the authors state, ‘’the study demonstrates that employing alternative metals in well-established homogeneous processes provides an opportunity to address challenges that are difficult to tackle with canonical catalysts’’. We, at InCatT B.V. underline this thought as this approach can lead to new innovations in the field of catalysis. Our approach is to screen large chemicals spaces with robotic high throughput equipment to quickly identify interesting catalyst leads. These leads are then further optimized using combined kinetic and DoE studies providing a wealth of information on detailed knowledge about the mechanism of the reaction but also identifying the window of operation. These insights are essential for fast upscaling and implementation of the new catalysis.

About InCatT ( InCatT B.V. is a company specialized in catalyst screening and catalyst development from initial catalyst-lead finding to process optimization. Over the years we have worked with different industries ranging from Flavor & Fragrance, Bio-based industry, Pharmaceutical and Bulk chemical industry to solve their most challenging projects.

Article: “Isoselective Hydroformylation of Propylene by Iodide-Assisted Palladium Catalysis”

By: Michel Sigrist,Dr. Yang Zhang,Dr. Cyril Antheaume,Dr. Paweł Dydio

Angewandte Chemie Communications Angew. Chem.Int. Ed.2022,e202116406