Hydroformylation (Oxo Process)

Understanding Key Mechanisms and Improve Catalytic Processes

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What Is Hydroformylation?

Hydroformylation, also known as oxo synthesis, is a chemical reaction involving the addition of carbon monoxide (CO) and hydrogen (H₂) to an unsaturated compound, typically an alkene or alkyne. The reaction is catalyzed by transition metal complexes, such as rhodium or cobalt, leading to the formation of aldehydes or aldehyde derivatives.

Hydroformylation plays a pivotal role in chemical synthesis by forming aldehyde compounds, which serve as building blocks for the production of various compounds such as alcohols, amines, and carboxylic acids. This process holds significant importance in the synthesis of bulk chemicals, making it a fundamental chemical reaction.

Furthermore, hydroformylation finds application in the chiral synthesis of intricate fine chemicals and pharmaceuticals. Catalysts with specific metal-ligand bonding are utilized to achieve this, enabling the synthesis of more complex compounds. Although hydroformylation is primarily associated with homogeneous catalysis, there have been advancements in heterogeneous hydroformylation systems. Notably, rhodium complexes supported on different scaffolds have been developed for this purpose.

Hydroformylation is the source for millions of tons of industrial chemicals that are produced each year. The large volumes of 1-alkene produced by the petrochemical industry help to drive the extensive use of hydroformylation for industrial chemical processes. Though most long-chain, branched-chain, and cyclic olefins can be hydroformylated, the most common starting chemicals are ethylene and propylene, which yield propionaldehyde, n-butyraldehyde, and iso-butyraldehyde. Propionaldehyde from ethylene can be hydrogenated to form plasticizers, such as diethyl phthalates and long carbon chain alcohols used as surfactants and detergents. There is considerable interest and effort in developing catalysts for asymmetric hydroformylations, resulting in the formation of enantiomer-specific aldehydes. These, in turn, are converted into a range of chiral-specific molecules containing different functional groups.

What Is the Hydroformylation Mechanism?

The process of hydroformylation involves several steps that lead to the formation of either linear or branched aldehydes. In most industrial applications, linear aldehydes are preferred, which has prompted the exploration of methods to enhance their production. A critical step in the formation of both types of aldehydes is the insertion of hydride and alkene ligands. The hydride can add to either the carbon atom within the double bond or the terminal carbon atom. When the hydride adds to the internal double-bond carbon, a linear aldehyde is formed, whereas an addition to the terminal carbon results in a branched aldehyde.

To favor the formation of linear aldehydes, one approach is to introduce bulkier ligands to the metal center. For instance, incorporating a trialkyl phosphine ligand (PR₃) into the HCo(CO)₄ catalyst significantly increases the ratio of linear to branched aldehydes that are produced. This strategy helps promote the desired outcome and optimize the hydroformylation process for specific applications. With respect to the catalyst, new cobalt and rhodium ligand-specific complexes/processes have been developed that enable hydroformylations to occur at lower pressures and temperatures, as well as yield longer catalyst lifetimes.

Furthermore, there is a significant effort in the development of catalysts and processes that control regioselectivity and enantioselectivity in asymmetric hydroformylations. Rhodium catalysts are generally more effective with respect to rate and can operate at lower temperatures and pressures than cobalt catalysts. However, newer organocobalt catalysts have been developed that approach the effectiveness of the far more costly rhodium complexes.

What Is Asymmetric Hydroformylation?

Asymmetric hydroformylation employs readily accessible alkenes and syngas to synthesize enantiomerically-enhanced aldehydes from which enantiospecific compounds with various functionalities can be further synthesized. There are challenges associated with asymmetric hydroformylation, such as depressed reaction rates that occur as a result of the lower reaction temperature required to achieve the desired selectivity. To minimize these issues, asymmetric hydroformylations require organometallic catalysts with ligands that are different than those used, for example, in hydrogenation reactions. Ligand classes for asymmetric hydroformylations include mixed phosphine/phosphite, diphosphites, phospholanes, etc.

In addition to the type of catalytic complex used, asymmetric hydroformylations are affected by reaction temperature and CO pressure, either or both potentially altering reaction kinetics. As an example, in asymmetric hydroformylation of styrene, using higher CO pressures favors the formation of branched isomers, whereas lower CO pressure results in linear isomers. In-situ FTIR and Raman spectroscopy are useful techniques for investigating the kinetics of asymmetric hydroformylations catalyzed by metals with novel ligands, as well as for determining the effect of reaction variables on achieved performance. A more complete understanding of the trade-offs between reaction rate and enantiospecificity aids in determining the optimum reaction variables for a specific catalyst complex.

Tandem Hydroformylation/Hydrogenation

Discover how researchers at the esteemed University of Tokyo have revolutionized the production of industrially significant n-alcohols. Their pioneering tandem hydroformylation/hydrogenation process promises remarkable advantages in terms of increased yields and simplified operations, making it a game-changer in the industrial sector.

We invite you to delve deeper into their remarkable findings by downloading our exclusive white paper. Inside, you'll uncover the meticulous research behind this groundbreaking method and how it leverages real-time, in-situ mid-FTIR reaction monitoring to unravel the catalyst activity and robustness.

Technology for Hydroformylation Reactions

In-situ FTIR and Raman Spectroscopy

spectrometers for hydroformylation reaction monitoring

Investigating Hydroformylation Catalysts and the Effect of Reaction Conditions on Reaction Performance

With respect to homogenous catalysts, in-situ molecular spectroscopy provides structural information on active reaction species present, some of which may be transient. By measuring carbonyl band shifts in rhodium and cobalt hydroformylation catalysts, substantial insight into the mechanism and catalytic pathways can be inferred. In-situ spectroscopy also directly measures the effect of reaction variables such as temperature and pressure on hydroformylation activity and selectivity. The diamond attenuated total reflectance (ATR) sensors associated with ATR-FTIR technology easily handle hydroformylation reaction conditions. Raman spectrometers can measure catalytic reactions non-invasively through quartz windows in pressure reactors. In either case, the information is obtained in real time without disturbing reaction conditions. Raman spectroscopy has proven useful in investigating heterogeneous hydroformylation reactions.

Learn more about FTIR and Raman Spectroscopy

Automated Lab Reactors with Pressure Vessels

Hydroformylation reactions often involve precise control of reaction conditions, such as temperature, pressure, and reaction time. Automated chemical reactor systems provide accurate and reliable control over these parameters, ensuring consistent and reproducible results. Oxo syntheses can be highly exothermic and require effective heat management. Automated reactors are equipped with advanced temperature control mechanisms, such as jacketed reactors or internal heat exchangers, to maintain optimal reaction conditions and prevent overheating.

The use of automated reactors allows for better process monitoring and data acquisition. Integrated sensors and probes enable real-time measurement of key reaction parameters, such as pressure, temperature, and gas flow rates. This data can be logged and analyzed, facilitating process optimization and troubleshooting. Furthermore, automation streamlines the overall workflow by automating various tasks, such as feeding reagents, initiating reactions, and sampling. This reduces human error, increases efficiency, and enhances safety by minimizing exposure to hazardous substances.

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Application Examples

Examples of Hydroformylation In Industry

Rhodium-BiPhePhos Catalyzed Hydroformylation Studied by Operando FTIR spectroscopy: Catalyst Activation and Rate Determining Step

ReactIR Shows Active Catalyst Species and Tracks Key Intermediates Providing Kinetic and Mechanistic Information

Andreas Jörke, Andreas Seidel-Morgenstern, Christof Hamel, “Rhodium-BiPhePhos catalyzed hydroformylation studied by operando FTIR spectroscopy: Catalyst activation and rate determining step”, J. Mol. Catalysis A: Chem., 2017, 426 Part A, 10-14n.

ReactIR measurements were performed on the hydroformylation of 1-decene by a rhodium catalyst having the diphosphite molecule, BiPhePhos, as a ligand. In-situ IR measurements of the transformation of the precursor Rh compound, Rh(acac)(CO)₂ to the activated HRh(BiPhePhos)(CO)₂ catalyst, were of special interest. This later complex was identified as the major catalyst intermediate as the hydroformylation proceeded, and catalyst degradation via oxidation was not observed since P=O bonds were not present in the IR spectra. The authors report that the turnover frequency indicates that the Rh-BiPhePhos catalyzed hydroformylation is first order with respect to 1-decene concentration and that the rate-determining step is the olefin coordination.

The precursor Rh complex exhibited Rh-CO bands at 2085 cm^-1 and 2014 cm^-1 and these bands disappear when BiPhePhos is introduced indicating the replacement of CO by the diphosphite ligand. After H₂ is introduced, CO vibrations at 2077 and 2017 are observed consistent with the literature assignments for the Rh-hydridodicarbonyl complex. When the olefin is injected, the C=C band at 1643 cm^-1 is observed, which disappears as the hydroformylation proceeds concurrently with the formation of the intense undecanal C=O band at 1729 cm^-1. The normalized ratio of these bands provides the conversion measurement of the 1-decene and the calculation of the turnover number.

Rh-catalyzed Hydroformylation of Butadiene to Adipaldehyde

ReactIR Provides Insight into Reaction Pathways, Catalyst Selectivity, and Activity

Si-min Yu, William Snavely, Raghunath V. Chaudhari, Bala Subramanian, “Butadiene hydroformylation to adipaldehyde with Rh-based catalysts: Insights into ligand effects”, Molec. Catalysis, 2020, 484, 110721

The authors report that butadiene hydroformylation to adipaldehyde via organorhodium catalysis is an option for producing C₆ compounds, such as adipic acid and hexamethylenediamine. For this reason, they sought to improve adipaldehyde yield by gaining insight into reaction pathways and to determine how reaction conditions affect activity and selectivity. Rh complexes with eight different ligands were systematically investigated using data acquired from in-situ IR measurements. They report that for the hydroformylation of butadiene at 80 °C and 14 bar syngas (molar CO/H₂ = 1) pressure, the ligand/Rh ratio, rhodium concentration, butadiene concentration and syngas pressure do not affect adipaldehyde selectivity. However, they found that the selectivity is highly dependent on the type of ligand employed and the bite angle of the ligand. Based on the ReactIR data, they propose that lower selectivity may result from the formation of the stable rhodium η³-crotyl complex with the various Rh complexes.

New Cobalt Hydroformylation Catalyst

ReactIR Provides Insight into Catalyst Species, Activity, and Stability

Drew M. Hood, Ryan A. Johnson, Alex E. Carpenter, Jarod M. Younker, David J. Vinyard, George G. Stanley, “Highly active cationic cobalt(II) hydroformylation catalysts”, Science, 2020, 367(6477), 542-548

The authors report the development of cobalt catalysts for the hydroformylation of alkenes to form aldehydes that are nearly as active as costly rhodium-based catalysts. These novel cationic cobalt(II) bisphosphine hydrido-carbonyl catalysts are hundreds of times more active than the original neutral cobalt catalysts, HCo(CO)₄ and HCo(CO)₃(PR₃) and operate under milder conditions such as lower pressures. They report that for simple linear alkenes, these catalysts have low linear-to-branched (L:B) regioselectivity, but high L:B selectivity for internal alkenes with alkyl branches. Furthermore, they find that the new catalysts are resistant to degradation and have long usable lifetimes.

In-situ IR measurements under actual reaction conditions reveal the presence of several active cationic catalyst species and provide insight into the stability of the catalyst as a function of time. ReactIR measurements show few changes in the carbonyl region of the spectra between 33 and 96 hours. The resulting catalyst solution was tested and found to be as effective for hexene hydroformylation as a fresh catalyst precursor sample.

Citations and References

Journal Articles on Hydroformylation Reactions

Below is a selection of hydroformylation reaction investigations in scientific publications.

Si-min Yu, William Snavely, Raghunath V. Chaudhari, Bala Subramanian, “Butadiene hydroformylation to adipaldehyde with Rh-based catalysts: Insights into ligand effects”, Molec. Catalysis, 2020, 484, 110721
Drew M. Hood, Ryan A. Johnson, Alex E. Carpenter, Jarod M. Younker, David J. Vinyard, George G. Stanley, “Highly active cationic cobalt(II) hydroformylation catalysts”, Science, 2020, 367(6477), 542-548
J. M. Dreimann, E. Kohls, H. F. W. Warmeling, M. Stein, L. F. Guo, M. Garland, T. N. Dinh, A. J. Vorholt, “In-situ infrared spectroscopy as a tool for monitoring molecular catalyst for hydroformylation in continuous processes”, ACS Catal., 2019, 9(5), 4308–4319
Andreas Jörke, Andreas Seidel-Morgenstern, Christof Hamel, “Rhodium-BiPhePhos catalyzed hydroformylation studied by operando FTIR spectroscopy: Catalyst activation and rate determining step”, J. Mol. Catalysis A: Chem., 2017, 426 Part A, 10-14
Hentschel, B., Kiedorf, G., Gerlach, M., Hamel, C., Seidel-Morgenstern, A., Freund, H., & Sundmacher, K. (2015). Model-Based Identification and Experimental Validation of the Optimal Reaction Route for the Hydroformylation of 1-Dodecene. Industrial & Engineering Chemistry Research, 54(6), 1755–1765. https://doi.org/10.1021/ie504388t
Sebastian Schmidt, Eszter Baráth, Christoph Larcher, Tobias Rosendahl, Peter Hofmann, “Rhodium-Catalyzed Hydroformylation of 1,3-Butadiene to Adipic Aldehyde: Revealing Selectivity and Rate-Determining Steps”, Organometallics 2015, 34, 5, 841–847
László T. Mika, László Orha, Eddie van Driessche, Ron Garton, Katalin Zih-Perényi, István T. Horváth, “Water-Soluble-Phosphines-Assisted Cobalt Separation in Cobalt-Catalyzed Hydroformylation”, Organometallics 2013, 32, 19, 5326–5332
Markert, J., Brunsch, Y., Munkelt, T., Kiedorf, G., Behr, A., Hamel, C., & Seidel-Morgenstern, A. (2013). Analysis of the reaction network for the Rh-catalyzed hydroformylation of 1-dodecene in a thermomorphic multicomponent solvent system. Applied Catalysis A-general, 462–463, 287–295. https://doi.org/10.1016/j.apcata.2013.04.005
Daniela Fuchs, Géraldine Rousseau, Lisa Diab, Urs Gellrich, Bernhard Breit, “Tandem Rhodium‐Catalyzed Hydroformylation–Hydrogenation of Alkenes by Employing a Cooperative Ligand System“, Angew. Chem. 2012, 51(9), 2178-2182
Jaroslav Keybl and Klavs F. Jensen “Microreactor System for High-Pressure Continuous Flow Homogeneous Catalysis Measurements”, Ind. Eng. Chem. Res. 2011, 50, 11013–11022
Benjamin Hentschel, Gregor Kiedorf, Martin Gerlach, Christof Hamel, Andreas Seidel-Morgenstern, Hannsjörg Freund, Kai Sundmacher, “Model-Based Identification and Experimental Validation of the Optimal Reaction Route for the Hydroformylation of 1‑Dodecene”, Ind. Eng. Chem. Res. 2015, 54, 1755−1765
Takahashi, K., Yamashita, M., & Nozaki, K. (2012). Tandem Hydroformylation/Hydrogenation of Alkenes to Normal Alcohols Using Rh/Ru Dual Catalyst or Ru Single Component Catalyst. Journal of the American Chemical Society, 134(45), 18746–18757. https://doi.org/10.1021/ja307998h

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What Is the Process of a Hydroformylation Reaction?

The hydroformylation reaction, also known as the oxo process, is a significant industrial process used for the synthesis of aldehydes from olefins (alkenes). The process involves the reaction of an olefin with carbon monoxide (CO) and hydrogen (H₂) in the presence of a catalyst, typically a transition metal complex.

The general process of hydroformylation can be described in several steps. Firstly, the olefin substrate reacts with the catalyst to form a metal-olefin complex. This step is often reversible and governs the rate of the reaction. The catalyst used can vary, but commonly employed catalysts include those based on cobalt, rhodium, and iridium. Next, the metal-olefin complex undergoes a series of reactions, including the insertion of CO and H₂ molecules. The insertion of CO forms a metal-carbonyl complex, while the insertion of H₂ leads to the formation of metal-hydride complexes. These steps are crucial for the subsequent transformations. In the following step, the metal-carbonyl complex interacts with the metal-hydride complex, leading to the formation of an aldehyde product. This step involves the migration of the metal-hydride group to the carbonyl carbon, resulting in the desired aldehyde. The specific pathway and mechanism of this migration depend on the reaction conditions and the nature of the catalyst. Finally, the aldehyde product is released from the catalyst, and the catalyst returns to its original state, ready for the next cycle of the reaction. The aldehydes produced through hydroformylation are valuable intermediates used in various industries, including the production of detergents, plastics, and pharmaceuticals.

What Are the Conditions for Hydroformylation Reactions?

Hydroformylation reactions require specific conditions to achieve efficient and selective conversion of olefins into aldehydes. The conditions can vary depending on the specific reaction and desired outcomes, but the following parameters play a crucial role in hydroformylation:

Temperature: Hydroformylation reactions typically occur at elevated temperatures, typically ranging from 80 to 200 degrees Celsius. The optimal temperature depends on the specific catalyst and substrate used.
Pressure: The reaction is carried out under high-pressure conditions to ensure the efficient dissolution of carbon monoxide (CO) and hydrogen (H₂) gases. Typical pressures range from several atmospheres to tens of atmospheres.
Catalyst: Catalysts are essential for promoting the hydroformylation reaction. Commonly used catalysts include transition metal complexes, such as rhodium, cobalt, and iridium complexes. The choice of catalyst depends on the specific substrate and desired reaction selectivity.
Solvent: Hydroformylation reactions are typically performed in a solvent to facilitate the mixing of reactants and maintain a homogeneous reaction mixture. Common solvents include polar organic solvents like alcohols or ethers.
CO and H₂ Ratio: The ratio of carbon monoxide to hydrogen is an essential factor in controlling the selectivity of the hydroformylation reaction. Varying the CO:H₂ ratio allows for the control of the linear-to-branched aldehyde ratio in the product.
Ligands: Ligands are often used in conjunction with the catalyst to modify its reactivity and selectivity. Ligands can influence the regioselectivity, stereochemistry, and stability of the catalyst, thereby affecting the reaction outcome.
Reaction Time: The reaction time required for hydroformylation can vary depending on the specific substrate and reaction conditions. Reactions typically proceed over several hours to achieve the desired conversion and selectivity.

It's important to note that the specific conditions may vary depending on the reaction system, catalyst, substrate, and desired product. Optimization of these conditions is crucial for achieving high yields and desired selectivity in hydroformylation reactions.

What Catalysts Are Used for Hydroformylation?

The choice of catalyst for hydroformylations is critical in determining the reaction's efficiency, selectivity, and overall success. Several catalysts are commonly used in hydroformylation reactions, including:

Rhodium-based Catalysts: Rhodium catalysts are widely employed in hydroformylation due to their high activity and selectivity. Examples of rhodium catalysts include RhCl(PPh₃)₃ (known as Wilkinson's catalyst) and its derivatives. These catalysts exhibit excellent regioselectivity, favoring the formation of linear aldehydes.
Cobalt-based Catalysts: Cobalt catalysts are another common choice for hydroformylation reactions. Notably, Co₂(CO)₈, known as cobalt tetracarbonyl, is a popular cobalt catalyst. Cobalt catalysts are more cost-effective compared to rhodium catalysts, although they generally exhibit lower selectivity.
Iridium-based Catalysts: Iridium complexes have shown promising catalytic activity in hydroformylation reactions. Catalysts such as [Ir(COD)(PCy₃)Cl] (COD = 1,5-cyclooctadiene, PCy₃ = tricyclohexylphosphine) have been employed for efficient hydroformylation processes.
Ruthenium-based Catalysts: Ruthenium complexes have gained attention for their potential in hydroformylation reactions. Catalysts like RuHCl(CO)(PPh₃)₃ have exhibited good selectivity in certain hydroformylation reactions.
Nickel-based Catalysts: Nickel catalysts have been investigated for hydroformylation, particularly in niche applications. Nickel carbonyl complexes, such as Ni(CO)4, have been utilized in specific hydroformylation processes.

These catalysts can be modified by incorporating various ligands, such as phosphines, phosphites, or phosphinites, to fine-tune their reactivity and selectivity. Ligands play a crucial role in controlling the regioselectivity of the reaction and modifying the catalyst's properties. The choice of catalyst depends on factors such as the desired product, substrate, reaction conditions, and cost considerations. Optimizing the catalyst selection and reaction conditions is essential to achieve high yields, desired selectivity, and economic feasibility in hydroformylation processes.

Are Hydroformylation Reactions Exothermic?

Hydroformylation reactions are typically exothermic in nature meaning they release heat during the reaction process. The exothermicity of hydroformylation reactions can be attributed to the chemical transformations occurring, which involve the breaking and forming of chemical bonds. The exothermic nature of hydroformylation can be understood by examining the bond energies involved. The breaking of the relatively weak π bond in the olefin and the formation of stronger σ bonds in the aldehyde and the intermediate metal complexes release energy. This energy is liberated as heat, leading to an increase in the overall temperature of the reaction system.

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