Enabling high-turnover methanol-to-syngas reforming

Enabling high-turnover methanol-to-syngas reforming | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Enabling high-turnover methanol-to-syngas reforming Troels Skrydstrup, Andreas Bonde, Gabriel Batista, Michal Gurský This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9102906/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Carbon-based feedstocks, including oil, coal, and natural gas, are essential raw materials for the chemical industry. This makes the transition away from fossil resources challenging compared to energy and transportation sectors. Renewable methanol has emerged as a promising liquid C1 platform that could provide a drop-in route to synthesis gas (syngas), a central intermediate in large-scale chemical production. However, homogeneous methanol-to-syngas reforming is typically performed in closed batch reactors, where accumulation of gaseous products rapidly suppresses catalytic turnover. Here we report a continuous flow system for homogeneous methanol-to-syngas reforming using Ru-MACHO-based catalysts that overcomes these limitations through continuous separation of gaseous products from the catalytic phase. Systematic optimisation using a design-of-experiments strategy identified the key operational parameters governing productivity, while ligand design enabled improved catalyst stability under flow conditions. The resulting system enables sustained syngas generation over extended operation and delivers substantially enhanced catalytic performance relative to batch operation. These findings demonstrate how combining reactor operation with molecular catalyst design can unlock new operating regimes for equilibrium-limited homogeneous catalytic transformations. Physical sciences/Chemistry/Catalysis Physical sciences/Chemistry/Green chemistry/Sustainability Physical sciences/Chemistry/Catalysis/Homogeneous catalysis Physical sciences/Chemistry/Chemical synthesis/Flow chemistry Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction The chemical industry underpins modern society but remains fundamentally dependent on fossil-derived feedstocks. 1 Unlike energy and transportation sectors, chemical manufacturing requires carbon as a molecular building block, rendering defossilisation uniquely challenging. 2 With the accelerating impacts of climate change already manifesting globally, urgent action is imperative. International agreements such as the Paris Agreement have intensified political pressure, but technological transformation remains essential. 3 The Stockholm Declaration on Chemistry for the Future calls for precisely such a paradigm shift; a reinvention of the chemical sciences analogous to the fossil-fuelled revolution of the twentieth century. 4 This new revolution must deliver the molecules and materials essential to modern society, while fundamentally decoupling chemical production from fossil carbon. 5,6 Achieving a transition from fossil carbon will require more than novel synthetic methods; it demands renewable feedstocks that can integrate into existing chemical value chains. Modern large-scale chemical manufacturing plants are built around highly optimised infrastructures that rely on standardised intermediates such as synthesis gas (syngas, H 2 /CO mixture), making redesign of downstream processes economically challenging. Consequently, drop-in technologies that deliver renewable carbon streams compatible with established process logic are particularly attractive. Among potential candidates, green methanol, produced from biomass or captured CO 2 , has emerged as a promising renewable platform for this transition. 7 As a liquid C 1 feedstock, methanol offers clear advantages in storage, transportation, and operational safety relative to gaseous alternatives, and its renewable production capacity is expanding at industrial scale. 8 Beyond its role as an energy carrier, methanol occupies a central position in chemical manufacturing, serving as a key precursor for multiple industrial intermediates. 9–11 Homogeneous catalytic reforming of methanol into syngas has therefore emerged as an attractive conceptual strategy, as it could allow renewable methanol to function as an upstream source for established carbonylation, hydroformylation, and Fischer–Tropsch processes. In contrast, direct syngas production via the reverse water–gas shift reaction (rWGS) remains energy intensive and continues to face challenges related to catalyst stability and process efficiency, highlighting the need for alternative approaches that leverage the rapidly expanding methanol infrastructure. 12,13 Leitner and co-workers previously demonstrated that the molecular catalyst Ru-MACHO Ph can catalyse methanol-to-syngas reforming in the absence of water ( Figure 1 a ). 14 However, under batch conditions, the authors demonstrated that catalytic turnover is limited by rapid accumulation of syngas in the reactor headspace, leading to early equilibration and suppressed activity. Periodic venting of the system only partially alleviated this limitation, affording turnover numbers (TONs) of up to 9230 for H 2 and 3150 for CO after 7 x 12 hours. Recent computational and microkinetic studies further indicate that methanol-to-syngas reforming is intrinsically constrained by reaction thermodynamics and liquid–vapour equilibrium, whereby gas accumulation alters catalyst resting-state populations and limits productivity. 15,16 These limitations are exacerbated by the volatility of methanol and key intermediates at the temperatures required for catalysis. One proposed solution involves direct coupling of syngas generation with downstream syngas consumption, as independently demonstrated by our research group in collaboration with the Beller team, 17 and Leitner et al . 17,18 While conceptually elegant, such tandem approaches require intricate co-optimisation of multiple catalytic systems and are fundamentally misaligned with industrial syngas utilisation, which relies on decoupled and independently optimised processes. Collectively, these observations suggest that overcoming current performance limitations will require not only catalyst redesign but also a fundamental reconsideration of reactor operation. Herein, we report a continuous flow system that enables syngas production via consecutive acceptorless dehydrogenation and decarbonylation of methanol using Ru-MACHO-based catalysts ( Figure 1 b ). By combining reactor engineering with catalyst design, the system overcomes equilibrium limitations inherent to batch operation by continuously removing gaseous products from the catalytic phase. Systematic optimisation using a Design of Experiments (DoE) approach led to sustained syngas generation with substantially enhanced cumulative productivity. Beyond performance gains, this work establishes a strategy in which catalyst operation and gas handling are deliberately decoupled, aligning syngas generation with industrial process logic and providing a scalable route to renewable syngas-derived commodity chemicals. Results and discussion Motivated by previous reports indicating limited catalytic turnover under batch operation, we first examined methanol-to-syngas reforming under conventional batch conditions to identify the factors limiting catalytic performance ( Figure 2 a ). Monitoring pressure evolution revealed rapid initial gas formation followed by early plateauing largely independent of catalyst loading, further corroborating with the previous reports that catalytic activity becomes constrained by gas accumulation. Additionally, operation at elevated temperature (150 °C), combined with the volatility of methanol and key intermediates, such as formaldehyde and methyl formate, introduces a second limitation. Under these conditions, continuous gas removal in a batch reactor would require repeated cooling–heating cycles to avoid loss of volatile components during venting. Thus, rendering sustained operation impractical, particularly at scales where the thermal mass of high-pressure reactors imposes substantial energy and process penalties. To overcome these intrinsic limitations of batch operation, we designed a continuous flow system capable of constantly separating gaseous products while recirculating the methanolic catalyst solution ( Figure 2 b ). This tubular reactor concept is designed to continuously remove gaseous products outside the heated zone, thereby mitigating product accumulation and minimising the loss of volatile key intermediates. The system employs an HPLC pump to circulate the catalytic solution through a pre-heated reaction loop (1.6 mL), where the methanol-to-syngas reforming occurs. The reaction mixture then passes through a cooled loop before entering a back-pressure regulator and a gravity-driven in-line gas–liquid separator, enabling continuous separation of syngas from the circulating liquid phase. Importantly, only the reaction mixture is heated and cooled, avoiding the thermal cycling of large reactor masses required under batch operation. To enable quantitative optimisation and real-time performance analysis, the stream exiting the back-pressure regulator was combined with a constant argon flow and analysed by inline gas chromatography (see SI for experimental details). The operational and chemical space was mapped using a DoE approach employing commercial Ru-MACHO Ph as benchmark catalyst. Guided by preliminary observations and prior studies, the tubular reactor temperature was fixed at 150 °C, while flow rate, back-pressure (BPR), solvent composition (methanol/toluene), and catalyst loading were systematically varied. The first DoE explored a broad operational window to identify the parameters governing syngas productivity and ratio (see SI for experimental details). This analysis revealed back-pressure as the dominant factor controlling catalytic output, while flow rate showed a substantial but less significant effect, and methanol dilution with toluene proved statistically insignificant. Notably, operation at low back-pressure dramatically increased syngas formation, whereas increasing the pressure suppressed productivity, consistent with a process governed by gas-liquid equilibrium. The minimal influence of toluene as co-solvent further indicates that catalyst performance is primarily governed by liquid–gas equilibrium rather than bulk solvent effects. A second DoE focused on narrowing the operational window and examining the interplay between catalyst loading, flow rate, and back-pressure ( Figure 3 a ). This analysis revealed a narrow pressure regime around 75–100 psi where high syngas productivity and H 2 /CO ratios were consistently achieved. Lower pressures resulted in unstable flow dynamics due to partial vaporisation of methanol and intermediates prior to the back-pressure regulator. Importantly, decreasing catalyst loading increased turnover numbers non-proportionally, as expected from the observed maximum pressures independent of catalyst loading in batch. Based on these results, conditions of 75 psi back-pressure and 2.5 mL/min flow rate were selected as robust conditions balancing productivity, reproducibility, and catalyst efficiency. These conditions were subsequently used for catalyst optimisation studies. Under the optimised conditions; Ru-MACHO Ph (2.0 or 0.20 µmol), t BuOK (200 µmol), and methanol (20 mL) at 75 psi, 2.5 mL min⁻¹, and 150 °C, the continuous flow system produced 51.5 mmol of H 2 and 24.5 mmol of CO within 6 hours, corresponding to TONs of 22535 and 11335, respectively. Unless otherwise stated, results are only shown for 2.0 µmol catalyst loading, while data for lower catalyst loadings are provided in the Supplementary Information (Page S20). Notably, this performance was highly reproducible across repeated experiments performed by different operators, underscoring the robustness and operational reliability of the flow system. Despite notably surpassing previously reported batch performances regarding total production, TONs and turnover frequencies (TOFs), significant catalyst deactivation was observed, with only 11.4% activity retention (AR), with respect to CO, after 6 hours ( Figure 3 b ). These observations suggest that catalyst stability is a major limitation under continuous operation. Catalyst deactivation pathways have been proposed for Ru-MACHO-based systems, including ligand decomposition ( Figure 3 c ). 16,20–24 Following activation of Ru-MACHO Ph using t BuOK to form the Ru-amido complex C1 , various complexes have been observed in solution, including C2 , C3 , and C4 . 14,16 While the Ru-methoxide complex C2 is proposed to be in a dynamic equilibrium with C1, and the Ru-dihydride complex C3 can undergo alcohol-assisted hydrogen release to reform C1 , the Ru-dicarbonyl complex C4 was proposed computationally by Nova et al . as a low-energy sink species. 16 Notably, Kayaki and co-workers reported that C4 remains catalytically active in the N -methylation of anilines proceeding via a hydrogen-borrowing mechanism. 25 Given the close similarity between Kayaki’s conditions, formation of C4 under the reaction conditions employed here is highly plausible. Rather than representing irreversible deactivation, C4 is therefore better described as a low-lying resting state, where accumulation of this species shifts catalyst speciation away from the productive cycle and lowers observed TOFs due to the energetic penalty required for re-entry into the active pathway as C1 . In line with this interpretation, Prakash and co-workers demonstrated that the reactivity of related Ru-dicarbonyl complexes depends on substrate identity and phosphine substitution, underscoring how electronic and steric effects influence both catalyst speciation and intrinsic reactivity. 26 However, the relevance of these species under methanol-to-syngas reforming remains unclear. Direct identification of inactive species proved challenging due to the highly dilute catalytic regime under continuous flow operation, and neither NMR spectroscopy nor HRMS analysis allowed unambiguous assignment of deactivation products. Alternatively, control experiments aimed at probing previously proposed pathways were therefore performed. Schneider and co-workers reported that [RuCl 2 PMe 3 (MACHO i Pr )] complexes can form an analogous of Ru-enamido complex C5 in the presence of excess t BuOK in aprotic solvents. 21,22 However, Beller and co-workers did not observe evidence for such species under basic aqueous methanol conditions, suggesting a dependence of catalyst speciation on reaction environment. 27 To probe whether dehydrogenated species could contribute to catalyst deactivation under continuous flow conditions, an experiment including Pd/C within the gas–liquid separator was performed (see SI for experimental details). 23,24 This resulted in decreased catalytic performance, likely due to non-selective adsorption of the homogeneous catalyst on activated carbon, and therefore did not provide direct evidence for this pathway. The tripodal Ru 0 -carbonyl complex C6 reported by Schaub et al . retained significant H 2 evolution but produced only limited CO under reaction conditions (see SI for experimental details). This behaviour indicates that alcohol dehydrogenation remains operative, whereas decarbonylation is inhibited, consistent with computationally proposed transition states for CO release. 16,20 Additional deactivation pathways involving ligand dehydrogenation have been proposed for related MACHO systems. The hetero-nuclear ruthenium complex C7 was neither synthesised nor assessed herein. Previous computational analyses postulated that catalyst modification alone should not improve catalytic turnovers under equilibrium-limited batch conditions. 16 Continuous flow operation, however, reduces the dominance of equilibrium constraints and enables intrinsic kinetic differences between catalyst variants to translate into differences in overall performance. We therefore hypothesised that ligand tailoring could modulate catalyst speciation and alter the energetics of key catalytic steps under these conditions. Guided by this premise, a systematic ligand scope was investigated (Figure 4). Initial modifications focused on substituents on the phosphine aryl groups, probing both electronic and steric effects. In general, deviations from the parent phenyl substituent resulted in reduced syngas productivity. Electron-rich derivatives, Ru-MACHO p (Me) and Ru-MACHO p (OMe) , as well as more sterically congested derivatives, Ru-MACHO p (iPr) and Ru-MACHO p (3-Pe) , showed slightly diminished syngas productivity. Electron-deficient Ru-MACHO p (CF3) expelled significantly lower activity, which afforded a 42% decrease in total syngas formation relative to Ru-MACHO Ph . Likewise, extension of the aromatic framework to naphthyl or biphenyl substituents resulted in poor solubility and lower overall activity. Notably, the meta-substituted Ru-MACHO m,m (Me) derivative displayed a distinct behaviour. While overall productivity after 6 h was only moderately improved, catalyst deactivation was significantly reduced, retaining 36.8% of the peak CO production rate compared with 11.4% for Ru-MACHO Ph . This observation suggests that subtle modifications of the ligand environment can significantly influence catalyst stability under continuous flow operation. Given the influence of steric and electronic effects observed within the aryl series, attention was next directed towards alkyl-substituted Ru-MACHO derivatives, which allows further systematic modulation of steric demand around the metal centre. Interestingly, a trade-off between catalytic activity and stability emerged across this series. Compared to Ru-MACHO Ph , Ru-MACHO Et exhibited 65.0% activity retention although with comparatively modest turnover numbers (H 2 : 12405, CO: 5650). Increasing steric bulk to Ru-MACHO i Pr substantially enhanced productivity (H 2 : 25370, CO: 12385), albeit at the expense of stability, with only 41.7% of the peak CO production rate maintained after 6 h. Interestingly, further increasing steric demand to cyclohexyl substituent, Ru-MACHO Cy produced a more balanced profile by combining high turnover numbers (H 2 : 24320, CO: 11423) with improved activity retention (62.1% after 6 h). In contrast, excessive steric encumbrance in tert -butyl and adamantyl derivatives (Ru-MACHO t Bu and Ru-MACHO Ad ) resulted in near-complete loss of activity, indicating that overly hindered environments likely impede access to the metal centre. Although these observations provide insight into catalyst speciation under flow conditions, the precise origin of long-term deactivation remains unresolved and is the subject of ongoing investigation. Encouraged by the stability of Ru-MACHO Cy , efforts were directed towards scaling the continuous flow system. More specifically, the tubular reactor volume was increased from 1.6 mL to 32 mL, thus increasing the fraction of catalyst solution constantly exposed to the heated section from ~8% to ~71%. To maintain stable operation and retain a constant concentration of Ru-MACHO Cy under these conditions, an additional HPLC pump was integrated with an automated feedback protocol that continuously adjusted methanol feed based on CO production (see SI for details). This automated methanol replenishment prevented reservoir depletion and enabled steady-state operation during long-term experiments. Following a minor re-optimisation (see SI for experimental details), the flow system delivered a continuous syngas stream over 84 hours when employing 4.0 ppm Ru-MACHO Cy ( Figure 5 ). The outcome was astonishing record turnover numbers of 269347 for H 2 and 130829 for CO, corresponding to average TOFs of 3207 and 1557, respectively. Importantly, the system achieved 47.5% activity retention relative to the post-induction steady-state regime (180 minutes). These results demonstrate that combining catalyst design with continuous flow operation enables sustained, high-turnover syngas generation from methanol, providing a modular and scalable strategy compatible with existing syngas-based chemical infrastructure. Conclusion We have presented a continuous flow system for on-demand syngas generation from methanol that overcomes key limitations associated with batch methanol-to-syngas reforming. Through continuous separation of gaseous products from the catalytic phase, the developed system decouples gas handling from catalyst operation, suppresses equilibrium limitations, and enables sustained catalytic turnover under mild conditions. Systematic optimisation using Design of Experiments, identified back-pressure as the dominant operational parameter controlling productivity, establishing a narrow operating regime in which efficient syngas formation at a H 2 /CO ratio of 2:1 was achieved. Although catalyst deactivation remains a central challenge, mechanistic control experiments and ligand modification studies revealed that catalyst speciation and stability can be strongly influenced by steric and electronic tuning of the MACHO scaffold. More specifically, a cyclohexyl-derivative, Ru-MACHO Cy , proved long-term catalyst stability under flow conditions, enabling continuous operation over extended timescales. Translation of the optimised system to a larger reactor configuration afforded sustained syngas production over 84 hours, reaching record turnover numbers for both hydrogen and carbon monoxide. Beyond performance improvements, this work demonstrates that reactor design and catalyst development must be considered together to unlock new operating regimes inaccessible under batch conditions. By aligning renewable methanol-to-syngas reforming with established syngas-demanding processes, this modular flow system provides a scalable strategy for integrating renewable syngas into existing chemical infrastructures. Methods See supplementary Information for further methods. Declarations Data Availability All reported data is available in the supplementary information. Acknowledgments We are deeply grateful to Heraeus Precious Metals GmbH & Co. KG, who supported this study by providing rhodium precursors. We also thank Prof. Dr. Kleber Thiago de Oliveira and Dr. Rodrigo Costa e Silva for the fruitful discussions. Funding We are grateful for financial support by Villum Fonden (Grant No. 71056, T.S.), Danish National Research Foundation (Grant No. DNRF118, T.S. and DNRF93), the Novo Nordisk Foundation (Grant no. NNF21SA0072700) and Aarhus University. Furthermore, support from the European Union’s Horizon 2020 research and innovation program under grant agreement No 862179 and Marie Sklodowska-Curie grant agreement No 859910 is also gratefully acknowledged. Author contributions Conceptualisation and writing/revising of the original draft were carried out by A.B., G.M.F.B. and T.S. Experiment design and experimental investigations were carried out by A.B., G.M.F.B. and M.G. Funding acquisition was carried out by T.S. All authors reviewed the final manuscript. Competing interests T.S. is co-owner of SyTracks A/S, which commercialises CO tubes. References Anastas, P. T. & Leitner, W. Transform the World through Chemistry. Angew. Chem. Int. Ed. 64 , e202512699 (2025). Euan Casey et al. Catalysing change: Defossilising the chemical industry – policy briefing. ISBN: 978-1-78252-705-3 Preprint at (2024). United Nations Framework Convention on Climate Change. The Paris Agreement. https://unfccc.int/sites/default/files/english_paris_agreement.pdf (2016). Welton, T. et al. Stockholm Declaration on Chemistry for the Future. RSC Sustain. 3 , 4187–4189 (2025). Lopez, G., Keiner, D., Fasihi, M., Koiranen, T. & Breyer, C. From fossil to green chemicals: sustainable pathways and new carbon feedstocks for the global chemical industry. Energy Environ. Sci. 16 , 2879–2909 (2023). Huo, J., Wang, Z., Oberschelp, C., Guillén-Gosálbez, G. & Hellweg, S. Net-zero transition of the global chemical industry with CO 2 -feedstock by 2050: feasible yet challenging. Green Chem. 25 , 415–430 (2023). Olah, G. A. Beyond Oil and Gas: The Methanol Economy. Angew. Chem. Int. Ed. 44 , 2636–2639 (2005). Kang, Seungwoo. Innovation Outlook: Renewable Methanol . (International Renewable Energy Agency, 2021). Sunley, G. J. & Watson, D. J. High productivity methanol carbonylation catalysis using iridium. Catal. Today 58 , 293–307 (2000). Tian, P., Wei, Y., Ye, M. & Liu, Z. Methanol to Olefins (MTO): From Fundamentals to Commercialization. ACS Catal. 5 , 1922–1938 (2015). Olsbye, U. et al. Conversion of Methanol to Hydrocarbons: How Zeolite Cavity and Pore Size Controls Product Selectivity. Angew. Chem. Int. Ed. 51 , 5810–5831 (2012). Becka, R., Bajohr, S. & Kolb, T. Review on CO 2 Activation via Catalytic Reverse Water‐Gas Shift Reaction. Chem. Ing. Tech. 97 , 860–881 (2025). Choi, Y. et al. Copper catalysts for CO 2 hydrogenation to CO through reverse water–gas shift reaction for e-fuel production: Fundamentals, recent advances, and prospects. Chem. Eng. J. 492 , 152283 (2024). Kaithal, A., Chatterjee, B., Werlé, C. & Leitner, W. Acceptorless Dehydrogenation of Methanol to Carbon Monoxide and Hydrogen using Molecular Catalysts. Angew. Chem. Int. Ed. 60 , 26500–26505 (2021). Yang, L. et al. Mechanistic Insight into Acceptorless Dehydrogenation of Methanol to Syngas Catalyzed by MACHO-Type Ruthenium and Manganese Complexes: A DFT Study. Inorg. Chem. 62 , 19516–19526 (2023). Liu, J. et al. Outer-Sphere CO Release Mechanism in the Methanol-to-Syngas Reaction Catalyzed by a Ru-PNP Pincer Complex. ACS Catal. 15 , 5113–5122 (2025). Bonde, A. et al. Integrating hydroformylations with methanol-to-syngas reforming. Chem 11 , 102396 (2025). Stahl, S., Vossen, J. T., Popp, S., Leitner, W. & Vorholt, A. J. Methanolation of Olefins: Low‐Pressure Synthesis of Alcohols by the Formal Addition of Methanol to Olefins. Angew. Chem. Int. Ed. 64 , e202418984 (2025). Tindall, D. J. et al. Ru 0 or Ru II : A Study on Stabilizing the “Activated” Form of Ru-PNP Complexes with Additional Phosphine Ligands in Alcohol Dehydrogenation and Ester Hydrogenation. Inorg. Chem. 59 , 5099–5115 (2020). Anaby, A. et al. Study of Precatalyst Degradation Leading to the Discovery of a New Ru 0 Precatalyst for Hydrogenation and Dehydrogenation. Organometallics 37 , 2193–2201 (2018). Friedrich, A., Drees, M., Käss, M., Herdtweck, E. & Schneider, S. Ruthenium Complexes with Cooperative PNP-Pincer Amine, Amido, Imine, and Enamido Ligands: Facile Ligand Backbone Functionalization Processes. Inorg. Chem. 49 , 5482–5494 (2010). Käß, M., Friedrich, A., Drees, M. & Schneider, S. Ruthenium Complexes with Cooperative PNP Ligands: Bifunctional Catalysts for the Dehydrogenation of Ammonia–Borane. Angew. Chem. Int. Ed. 48 , 905–907 (2009). Nguyen, D. H. et al. Deeper Mechanistic Insight into Ru Pincer-Mediated Acceptorless Dehydrogenative Coupling of Alcohols: Exchanges, Intermediates, and Deactivation Species. ACS Catal. 8 , 4719–4734 (2018). Zhang, L. et al. Catalytic Conversion of Alcohols into Carboxylic Acid Salts in Water: Scope, Recycling, and Mechanistic Insights. ChemSusChem 9 , 1413–1423 (2016). Ogata, O., Nara, H., Fujiwhara, M., Matsumura, K. & Kayaki, Y. N -Monomethylation of Aromatic Amines with Methanol via PNP-Pincer Ru Catalysts. Org. Lett. 20 , 3866–3870 (2018). Kar, S. et al. Mechanistic Insights into Ruthenium-Pincer-Catalyzed Amine-Assisted Homogeneous Hydrogenation of CO 2 to Methanol. J. Am. Chem. Soc. 141 , 3160–3170 (2019). Alberico, E. et al. Unravelling the Mechanism of Basic Aqueous Methanol Dehydrogenation Catalyzed by Ru–PNP Pincer Complexes. J. Am. Chem. Soc. 138 , 14890–14904 (2016). Additional Declarations Yes there is potential Competing Interest. Troels Skrydstrup is co-owner of SyTracks A/S, which commercialises CO tubes. Supplementary Files SISkrydstrup.pdf The supplementary information Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9102906","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":604958160,"identity":"31eee076-3dde-456a-8eae-7769ac02d6d3","order_by":0,"name":"Troels Skrydstrup","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAApElEQVRIiWNgGAWjYFAC5gPMMKZkAzEaeBjYEkjWwmNAohZ7/jMfPxdUbGPgn5HAeHMGUbZI5G6WnnHmNoPEjQRmyw3EaeHdxszbdpuB4UYCm+QDorTwn3nGzPvvNoM88VoYctiYeRtuMxiAtBDnsBtpxtI8x27zGJ552GxJlPfZ+w8//MxTc1tO7njywZs9xGhBOJCBsYEUDaNgFIyCUTAK8AEAjeQuKJljxtYAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0001-8090-5050","institution":"Aarhus University","correspondingAuthor":true,"prefix":"","firstName":"Troels","middleName":"","lastName":"Skrydstrup","suffix":""},{"id":604958161,"identity":"74113a10-b865-4e09-b0f3-d5b36d135674","order_by":1,"name":"Andreas Bonde","email":"","orcid":"","institution":"Aarhus University","correspondingAuthor":false,"prefix":"","firstName":"Andreas","middleName":"","lastName":"Bonde","suffix":""},{"id":604958162,"identity":"7f71a008-95c3-4c40-9204-a771988932c2","order_by":2,"name":"Gabriel Batista","email":"","orcid":"https://orcid.org/0000-0003-0541-9065","institution":"Aarhus University","correspondingAuthor":false,"prefix":"","firstName":"Gabriel","middleName":"","lastName":"Batista","suffix":""},{"id":604958163,"identity":"d3f34f87-6258-4e40-83a2-3f37811c9d6e","order_by":3,"name":"Michal Gurský","email":"","orcid":"","institution":"Slovak University of Technology","correspondingAuthor":false,"prefix":"","firstName":"Michal","middleName":"","lastName":"Gurský","suffix":""}],"badges":[],"createdAt":"2026-03-12 09:25:32","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9102906/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9102906/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":105794645,"identity":"b9c86e6e-3b76-4823-9796-4b13a036e921","added_by":"auto","created_at":"2026-03-31 08:30:15","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":134503,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ea \u003c/strong\u003ePrevious reports on homogeneous methanol-to-syngas reforming in batch. \u003cstrong\u003eb\u003c/strong\u003e This work, continuous methanol-to-syngas reforming in flow.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-9102906/v1/f4f36103cb52fc613a89c92e.png"},{"id":105794647,"identity":"8a343450-23fd-4ad8-bce2-3abeb16548c5","added_by":"auto","created_at":"2026-03-31 08:30:15","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":444079,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ea\u003c/strong\u003e Reaction conditions and pressure response over time for methanol-to-syngas reforming in batch with varying Ru-MACHO\u003csup\u003ePh\u003c/sup\u003e loadings. \u003cstrong\u003eb\u003c/strong\u003e The developed continuous flow system and a schematisation thereof.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-9102906/v1/ab4900d154aaac9cad107455.png"},{"id":105904048,"identity":"a6af16b1-086d-4304-835a-7c37999e1a59","added_by":"auto","created_at":"2026-04-01 10:02:43","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":150017,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ea\u003c/strong\u003e Selected contour plots for the second DoE displaying syngas production and ratio for flow rate against back-pressure. \u003cstrong\u003eb\u003c/strong\u003e Time-dependent catalytic activity and syngas ratio using optimised reaction conditions and Ru-MACHO\u003csup\u003ePh\u003c/sup\u003e (2.0 μmol). \u003cstrong\u003ec\u003c/strong\u003e Proposed complexes.\u003csup\u003e14,16,19–22\u003c/sup\u003e\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-9102906/v1/1f8c463c9c9bf97236bfe762.png"},{"id":105794649,"identity":"5d113890-fd43-4ac9-91ed-965e6a84ecc9","added_by":"auto","created_at":"2026-03-31 08:30:15","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":108220,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ea\u003c/strong\u003e Scope of Ru-MACHO-derivatives. \u003cstrong\u003eb\u003c/strong\u003e Time-dependent catalytic activity, showing only CO TOFs (see SI for experimental details).\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-9102906/v1/b76ad6004f6329f114d6a2e2.png"},{"id":106092929,"identity":"a945e58c-02f2-4d1a-8c31-b970d081cf16","added_by":"auto","created_at":"2026-04-03 11:30:48","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":93475,"visible":true,"origin":"","legend":"\u003cp\u003eReaction conditions for scaled flow system along with time-dependent catalytic activity and cumulative syngas production and ratio over time (see SI for experimental details).\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-9102906/v1/9f4dff73a8ee11a2fc718f70.png"},{"id":106095540,"identity":"93f0f26c-0879-44fc-8c0f-5dbb6577222f","added_by":"auto","created_at":"2026-04-03 11:48:50","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1251704,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9102906/v1/cb38da6b-7662-495a-bb3f-87502007b0f9.pdf"},{"id":105794646,"identity":"6ef8ab76-f16a-4b1c-8756-812c938abfc4","added_by":"auto","created_at":"2026-03-31 08:30:15","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":5677522,"visible":true,"origin":"","legend":"The supplementary information","description":"","filename":"SISkrydstrup.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9102906/v1/91f01964a71856a3f317ff24.pdf"}],"financialInterests":"\u003cb\u003eYes\u003c/b\u003e there is potential Competing Interest.\nTroels Skrydstrup is co-owner of SyTracks A/S, which commercialises CO tubes.","formattedTitle":"Enabling high-turnover methanol-to-syngas reforming","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe chemical industry underpins modern society but remains fundamentally dependent on fossil-derived feedstocks.\u003csup\u003e1\u003c/sup\u003e Unlike energy and transportation sectors, chemical manufacturing requires carbon as a molecular building block, rendering defossilisation uniquely challenging.\u003csup\u003e2\u003c/sup\u003e With the accelerating impacts of climate change already manifesting globally, urgent action is imperative. International agreements such as the \u003cem\u003eParis Agreement\u003c/em\u003e have intensified political pressure, but technological transformation remains essential.\u003csup\u003e3\u003c/sup\u003e The \u003cem\u003eStockholm Declaration on Chemistry for the Future\u003c/em\u003e calls for precisely such a paradigm shift; a reinvention of the chemical sciences analogous to the fossil-fuelled revolution of the twentieth century.\u003csup\u003e4\u003c/sup\u003e This new revolution must deliver the molecules and materials essential to modern society, while fundamentally decoupling chemical production from fossil carbon.\u003csup\u003e5,6\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eAchieving a transition from fossil carbon will require more than novel synthetic methods; it demands renewable feedstocks that can integrate into existing chemical value chains. Modern large-scale chemical manufacturing plants are built around highly optimised infrastructures that rely on standardised intermediates such as synthesis gas (syngas, H\u003csub\u003e2\u003c/sub\u003e/CO mixture), making redesign of downstream processes economically challenging. Consequently, drop-in technologies that deliver renewable carbon streams compatible with established process logic are particularly attractive. Among potential candidates, green methanol, produced from biomass or captured CO\u003csub\u003e2\u003c/sub\u003e, has emerged as a promising renewable platform for this transition.\u003csup\u003e7\u003c/sup\u003e As a liquid C\u003csub\u003e1\u003c/sub\u003e feedstock, methanol offers clear advantages in storage, transportation, and operational safety relative to gaseous alternatives, and its renewable production capacity is expanding at industrial scale.\u003csup\u003e8\u003c/sup\u003e Beyond its role as an energy carrier, methanol occupies a central position in chemical manufacturing, serving as a key precursor for multiple industrial intermediates.\u003csup\u003e9–11\u003c/sup\u003e Homogeneous catalytic reforming of methanol into syngas has therefore emerged as an attractive conceptual strategy, as it could allow renewable methanol to function as an upstream source for established carbonylation, hydroformylation, and Fischer–Tropsch processes. In contrast, direct syngas production via the reverse water–gas shift reaction (rWGS) remains energy intensive and continues to face challenges related to catalyst stability and process efficiency, highlighting the need for alternative approaches that leverage the rapidly expanding methanol infrastructure.\u003csup\u003e12,13\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eLeitner and co-workers previously demonstrated that the molecular catalyst Ru-MACHO\u003csup\u003ePh\u003c/sup\u003e can catalyse methanol-to-syngas reforming in the absence of water (\u003cstrong\u003eFigure 1\u003c/strong\u003e\u003cstrong\u003ea\u003c/strong\u003e).\u003csup\u003e14\u003c/sup\u003e However, under batch conditions, the authors demonstrated that catalytic turnover is limited by rapid accumulation of syngas in the reactor headspace, leading to early equilibration and suppressed activity. Periodic venting of the system only partially alleviated this limitation, affording turnover numbers (TONs) of up to 9230 for H\u003csub\u003e2\u003c/sub\u003e and 3150 for CO after 7 x 12 hours. Recent computational and microkinetic studies further indicate that methanol-to-syngas reforming is intrinsically constrained by reaction thermodynamics and liquid–vapour equilibrium, whereby gas accumulation alters catalyst resting-state populations and limits productivity.\u003csup\u003e15,16\u003c/sup\u003e These limitations are exacerbated by the volatility of methanol and key intermediates at the temperatures required for catalysis. One proposed solution involves direct coupling of syngas generation with downstream syngas consumption, as independently demonstrated by our research group in collaboration with the Beller team,\u003csup\u003e17\u003c/sup\u003e and Leitner \u003cem\u003eet al\u003c/em\u003e.\u003csup\u003e17,18\u003c/sup\u003e While conceptually elegant, such tandem approaches require intricate co-optimisation of multiple catalytic systems and are fundamentally misaligned with industrial syngas utilisation, which relies on decoupled and independently optimised processes. Collectively, these observations suggest that overcoming current performance limitations will require not only catalyst redesign but also a fundamental reconsideration of reactor operation.\u003c/p\u003e\n\u003cp\u003eHerein, we report a continuous flow system that enables syngas production via consecutive acceptorless dehydrogenation and decarbonylation of methanol using Ru-MACHO-based catalysts (\u003cstrong\u003eFigure 1\u003c/strong\u003e\u003cstrong\u003eb\u003c/strong\u003e). By combining reactor engineering with catalyst design, the system overcomes equilibrium limitations inherent to batch operation by continuously removing gaseous products from the catalytic phase. Systematic optimisation using a Design of Experiments (DoE) approach led to sustained syngas generation with substantially enhanced cumulative productivity. Beyond performance gains, this work establishes a strategy in which catalyst operation and gas handling are deliberately decoupled, aligning syngas generation with industrial process logic and providing a scalable route to renewable syngas-derived commodity chemicals.\u003c/p\u003e"},{"header":"Results and discussion","content":"\u003cp\u003eMotivated by previous reports indicating limited catalytic turnover under batch operation, we first examined methanol-to-syngas reforming under conventional batch conditions to identify the factors limiting catalytic performance (\u003cstrong\u003eFigure 2\u003c/strong\u003e\u003cstrong\u003ea\u003c/strong\u003e). Monitoring pressure evolution revealed rapid initial gas formation followed by early plateauing largely independent of catalyst loading, further corroborating with the previous reports that catalytic activity becomes constrained by gas accumulation. Additionally, operation at elevated temperature (150 °C), combined with the volatility of methanol and key intermediates, such as formaldehyde and methyl formate, introduces a second limitation. Under these conditions, continuous gas removal in a batch reactor would require repeated cooling–heating cycles to avoid loss of volatile components during venting. Thus, rendering sustained operation impractical, particularly at scales where the thermal mass of high-pressure reactors imposes substantial energy and process penalties.\u003c/p\u003e\n\u003cp\u003eTo overcome these intrinsic limitations of batch operation, we designed a continuous flow system capable of constantly separating gaseous products while recirculating the methanolic catalyst solution\u003cstrong\u003e\u0026nbsp;(\u003c/strong\u003e\u003cstrong\u003eFigure 2\u003c/strong\u003e\u003cstrong\u003eb\u003c/strong\u003e). This tubular reactor concept is designed to continuously remove gaseous products outside the heated zone, thereby mitigating product accumulation and minimising the loss of volatile key intermediates. The system employs an HPLC pump to circulate the catalytic solution through a pre-heated reaction loop (1.6 mL), where the methanol-to-syngas reforming occurs. The reaction mixture then passes through a cooled loop before entering a back-pressure regulator and a gravity-driven in-line gas–liquid separator, enabling continuous separation of syngas from the circulating liquid phase. Importantly, only the reaction mixture is heated and cooled, avoiding the thermal cycling of large reactor masses required under batch operation. To enable quantitative optimisation and real-time performance analysis, the stream exiting the back-pressure regulator was combined with a constant argon flow and analysed by inline gas chromatography (see SI for experimental details).\u003c/p\u003e\n\u003cp\u003eThe operational and chemical space was mapped using a DoE approach employing commercial Ru-MACHO\u003csup\u003ePh\u003c/sup\u003e as benchmark catalyst. Guided by preliminary observations and prior studies, the tubular reactor temperature was fixed at 150 °C, while flow rate, back-pressure (BPR), solvent composition (methanol/toluene), and catalyst loading were systematically varied. The first DoE explored a broad operational window\u0026nbsp;to identify the parameters governing syngas productivity and ratio (see SI for experimental details). This analysis revealed back-pressure as the dominant factor controlling catalytic output, while flow rate showed a substantial but less significant effect, and methanol dilution with toluene proved statistically insignificant. Notably, operation at low back-pressure dramatically increased syngas formation, whereas increasing the pressure suppressed productivity, consistent with a process governed by gas-liquid equilibrium. \u0026nbsp;The minimal influence of toluene as co-solvent further indicates that catalyst performance is primarily governed by liquid–gas equilibrium rather than bulk solvent effects.\u003c/p\u003e\n\u003cp\u003eA second DoE focused on narrowing the operational window and examining the interplay between catalyst loading, flow rate, and back-pressure (\u003cstrong\u003eFigure 3\u003c/strong\u003e\u003cstrong\u003ea\u003c/strong\u003e). This analysis revealed a narrow pressure regime around 75–100 psi where high syngas productivity and H\u003csub\u003e2\u003c/sub\u003e/CO ratios were consistently achieved. Lower pressures resulted in unstable flow dynamics due to partial vaporisation of methanol and intermediates prior to the back-pressure regulator. Importantly, decreasing catalyst loading increased turnover numbers non-proportionally, as expected from the observed maximum pressures independent of catalyst loading in batch. Based on these results, conditions of 75 psi back-pressure and 2.5 mL/min flow rate were selected as robust conditions balancing productivity, reproducibility, and catalyst efficiency. These conditions were subsequently used for catalyst optimisation studies.\u003c/p\u003e\n\u003cp\u003eUnder the optimised conditions; Ru-MACHO\u003csup\u003ePh\u003c/sup\u003e (2.0 or 0.20 µmol), \u003cem\u003et\u003c/em\u003eBuOK (200 µmol), and methanol (20 mL) at 75 psi, 2.5 mL min⁻¹, and 150 °C, the continuous flow system produced 51.5 mmol of H\u003csub\u003e2\u003c/sub\u003e and 24.5 mmol of CO within 6 hours, corresponding to TONs of 22535 and 11335, respectively. Unless otherwise stated, results are only shown for 2.0 µmol catalyst loading, while data for lower catalyst loadings are provided in the Supplementary Information (Page S20). Notably, this performance was highly reproducible across repeated experiments performed by different operators, underscoring the robustness and operational reliability of the flow system. Despite notably surpassing previously reported batch performances regarding total production, TONs and turnover frequencies (TOFs), significant catalyst deactivation was observed, with only 11.4% activity retention (AR), with respect to CO, after 6 hours (\u003cstrong\u003eFigure 3\u003c/strong\u003e\u003cstrong\u003eb\u003c/strong\u003e). These observations suggest that catalyst stability is a major limitation under continuous operation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCatalyst deactivation pathways have been proposed for Ru-MACHO-based systems, including ligand decomposition (\u003cstrong\u003eFigure 3\u003c/strong\u003e\u003cstrong\u003ec\u003c/strong\u003e).\u003csup\u003e16,20–24\u003c/sup\u003e Following activation of Ru-MACHO\u003csup\u003ePh\u003c/sup\u003e using \u003cem\u003et\u003c/em\u003eBuOK to form the Ru-amido complex \u003cstrong\u003eC1\u003c/strong\u003e, various complexes have been observed in solution, including \u003cstrong\u003eC2\u003c/strong\u003e, \u003cstrong\u003eC3\u003c/strong\u003e, and \u003cstrong\u003eC4\u003c/strong\u003e.\u003csup\u003e14,16\u003c/sup\u003e While the Ru-methoxide complex \u003cstrong\u003eC2\u003c/strong\u003e is proposed to be in a dynamic equilibrium with \u003cstrong\u003eC1,\u003c/strong\u003e and the Ru-dihydride complex \u003cstrong\u003eC3\u003c/strong\u003e can undergo alcohol-assisted hydrogen release to reform \u003cstrong\u003eC1\u003c/strong\u003e, the Ru-dicarbonyl complex \u003cstrong\u003eC4\u003c/strong\u003e was proposed computationally by Nova \u003cem\u003eet al\u003c/em\u003e. as a low-energy sink species.\u003csup\u003e16\u003c/sup\u003e Notably, Kayaki and co-workers reported that \u003cstrong\u003eC4\u003c/strong\u003e remains catalytically active in the \u003cem\u003eN\u003c/em\u003e-methylation of anilines proceeding via a hydrogen-borrowing mechanism.\u003csup\u003e25\u003c/sup\u003e Given the close similarity between Kayaki’s conditions, formation of \u003cstrong\u003eC4\u003c/strong\u003e under the reaction conditions employed here is highly plausible. Rather than representing irreversible deactivation, \u003cstrong\u003eC4\u003c/strong\u003e is therefore better described as a low-lying resting state, where accumulation of this species shifts catalyst speciation away from the productive cycle and lowers observed TOFs due to the energetic penalty required for re-entry into the active pathway as \u003cstrong\u003eC1\u003c/strong\u003e. In line with this interpretation, Prakash and co-workers demonstrated that the reactivity of related Ru-dicarbonyl complexes depends on substrate identity and phosphine substitution, underscoring how electronic and steric effects influence both catalyst speciation and intrinsic reactivity.\u003csup\u003e26\u003c/sup\u003e However, the relevance of these species under methanol-to-syngas reforming remains unclear. Direct identification of inactive species proved challenging due to the highly dilute catalytic regime under continuous flow operation, and neither NMR spectroscopy nor HRMS analysis allowed unambiguous assignment of deactivation products.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAlternatively, control experiments aimed at probing previously proposed pathways were therefore performed. Schneider and co-workers reported that [RuCl\u003csub\u003e2\u003c/sub\u003ePMe\u003csub\u003e3\u003c/sub\u003e(MACHO\u003cem\u003e\u003csup\u003ei\u003c/sup\u003e\u003c/em\u003e\u003csup\u003ePr\u003c/sup\u003e)] complexes can form an analogous of Ru-enamido complex \u003cstrong\u003eC5\u003c/strong\u003e in the presence of excess \u003cem\u003et\u003c/em\u003eBuOK in aprotic solvents.\u003csup\u003e21,22\u003c/sup\u003e However, Beller and co-workers did not observe evidence for such species under basic aqueous methanol conditions, suggesting a dependence of catalyst speciation on reaction environment.\u003csup\u003e27\u003c/sup\u003e To probe whether dehydrogenated species could contribute to catalyst deactivation under continuous flow conditions, an experiment including Pd/C within the gas–liquid separator was performed (see SI for experimental details).\u003csup\u003e23,24\u003c/sup\u003e This resulted in decreased catalytic performance, likely due to non-selective adsorption of the homogeneous catalyst on activated carbon, and therefore did not provide direct evidence for this pathway. The tripodal Ru\u003csup\u003e0\u003c/sup\u003e-carbonyl complex \u003cstrong\u003eC6\u003c/strong\u003e reported by Schaub \u003cem\u003eet al\u003c/em\u003e. retained significant H\u003csub\u003e2\u003c/sub\u003e evolution but produced only limited CO under reaction conditions (see SI for experimental details). This behaviour indicates that alcohol dehydrogenation remains operative, whereas decarbonylation is inhibited, consistent with computationally proposed transition states for CO release.\u003csup\u003e16,20\u003c/sup\u003e Additional deactivation pathways involving ligand dehydrogenation have been proposed for related MACHO systems. The hetero-nuclear ruthenium complex \u003cstrong\u003eC7\u003c/strong\u003e was neither synthesised nor assessed herein.\u003c/p\u003e\n\u003cp\u003ePrevious computational analyses postulated that catalyst modification alone should not improve catalytic turnovers under equilibrium-limited batch conditions.\u003csup\u003e16\u003c/sup\u003e Continuous flow operation, however, reduces the dominance of equilibrium constraints and enables intrinsic kinetic differences between catalyst variants to translate into differences in overall performance. We therefore hypothesised that ligand tailoring could modulate catalyst speciation and alter the energetics of key catalytic steps under these conditions. Guided by this premise, a systematic ligand scope was investigated (Figure 4). Initial modifications focused on substituents on the phosphine aryl groups, probing both electronic and steric effects. In general, deviations from the parent phenyl substituent resulted in reduced syngas productivity. Electron-rich derivatives, Ru-MACHO\u003cem\u003e\u003csup\u003ep\u003c/sup\u003e\u003c/em\u003e\u003csup\u003e(Me)\u003c/sup\u003e and Ru-MACHO\u003cem\u003e\u003csup\u003ep\u003c/sup\u003e\u003c/em\u003e\u003csup\u003e(OMe)\u003c/sup\u003e, as well as more sterically congested derivatives, Ru-MACHO\u003cem\u003e\u003csup\u003ep\u003c/sup\u003e\u003c/em\u003e\u003csup\u003e(iPr)\u003c/sup\u003e and Ru-MACHO\u003cem\u003e\u003csup\u003ep\u003c/sup\u003e\u003c/em\u003e\u003csup\u003e(3-Pe)\u003c/sup\u003e, showed slightly diminished syngas productivity. Electron-deficient Ru-MACHO\u003cem\u003e\u003csup\u003ep\u003c/sup\u003e\u003c/em\u003e\u003csup\u003e(CF3)\u003c/sup\u003e expelled significantly lower activity, which afforded a 42% decrease in total syngas formation relative to Ru-MACHO\u003csup\u003ePh\u003c/sup\u003e. Likewise, extension of the aromatic framework to naphthyl or biphenyl substituents resulted in poor solubility and lower overall activity. Notably, the meta-substituted Ru-MACHO\u003cem\u003e\u003csup\u003em,m\u003c/sup\u003e\u003c/em\u003e\u003csup\u003e(Me)\u003c/sup\u003e derivative displayed a distinct behaviour. While overall productivity after 6 h was only moderately improved, catalyst deactivation was significantly reduced, retaining 36.8% of the peak CO production rate compared with 11.4% for Ru-MACHO\u003csup\u003ePh\u003c/sup\u003e. This observation suggests that subtle modifications of the ligand environment can significantly influence catalyst stability under continuous flow operation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGiven the influence of steric and electronic effects observed within the aryl series, attention was next directed towards alkyl-substituted Ru-MACHO derivatives, which allows further systematic modulation of steric demand around the metal centre. Interestingly, a trade-off between catalytic activity and stability emerged across this series. Compared to Ru-MACHO\u003csup\u003ePh\u003c/sup\u003e, Ru-MACHO\u003csup\u003eEt\u003c/sup\u003e exhibited 65.0% activity retention although with comparatively modest turnover numbers (H\u003csub\u003e2\u003c/sub\u003e: 12405, CO: 5650). Increasing steric bulk to Ru-MACHO\u003cem\u003e\u003csup\u003ei\u003c/sup\u003e\u003c/em\u003e\u003csup\u003ePr\u003c/sup\u003e substantially enhanced productivity (H\u003csub\u003e2\u003c/sub\u003e: 25370, CO: 12385), albeit at the expense of stability, with only 41.7% of the peak CO production rate maintained after 6 h. Interestingly, further increasing steric demand to cyclohexyl substituent, Ru-MACHO\u003csup\u003eCy\u003c/sup\u003e produced a more balanced profile by combining high turnover numbers (H\u003csub\u003e2\u003c/sub\u003e: 24320, CO: 11423) with improved activity retention (62.1% after 6 h). In contrast, excessive steric encumbrance in \u003cem\u003etert\u003c/em\u003e-butyl and adamantyl derivatives (Ru-MACHO\u003cem\u003e\u003csup\u003et\u003c/sup\u003e\u003c/em\u003e\u003csup\u003eBu\u003c/sup\u003e and Ru-MACHO\u003csup\u003eAd\u003c/sup\u003e) resulted in near-complete loss of activity, indicating that overly hindered environments likely impede access to the metal centre. Although these observations provide insight into catalyst speciation under flow conditions, the precise origin of long-term deactivation remains unresolved and is the subject of ongoing investigation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eEncouraged by the stability of Ru-MACHO\u003csup\u003eCy\u003c/sup\u003e, efforts were directed towards scaling the continuous flow system. More specifically, the tubular reactor volume was increased from 1.6 mL to 32 mL, thus increasing the fraction of catalyst solution constantly exposed to the heated section from ~8% to ~71%. To maintain stable operation and retain a constant concentration of Ru-MACHO\u003csup\u003eCy\u003c/sup\u003e under these conditions, an additional HPLC pump was integrated with an automated feedback protocol that continuously adjusted methanol feed based on CO production (see SI for details).\u0026nbsp;This automated methanol replenishment prevented reservoir depletion and enabled steady-state operation during long-term experiments. Following a minor re-optimisation (see SI for experimental details), the flow system delivered a continuous syngas stream over 84 hours when employing 4.0 ppm Ru-MACHO\u003csup\u003eCy\u003c/sup\u003e (\u003cstrong\u003eFigure 5\u003c/strong\u003e). The outcome was astonishing record turnover numbers of 269347 for H\u003csub\u003e2\u003c/sub\u003e and 130829 for CO, corresponding to average TOFs of 3207 and 1557, respectively. Importantly, the system achieved 47.5% activity retention relative to the post-induction steady-state regime (180 minutes). These results demonstrate that combining catalyst design with continuous flow operation enables sustained, high-turnover syngas generation from methanol, providing a modular and scalable strategy compatible with existing syngas-based chemical infrastructure.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eWe have presented a continuous flow system for on-demand syngas generation from methanol that overcomes key limitations associated with batch methanol-to-syngas reforming. Through continuous separation of gaseous products from the catalytic phase, the developed system decouples gas handling from catalyst operation, suppresses equilibrium limitations, and enables sustained catalytic turnover under mild conditions. Systematic optimisation using Design of Experiments, identified back-pressure as the dominant operational parameter controlling productivity, establishing a narrow operating regime in which efficient syngas formation at a H\u003csub\u003e2\u003c/sub\u003e/CO ratio of 2:1 was achieved. Although catalyst deactivation remains a central challenge, mechanistic control experiments and ligand modification studies revealed that catalyst speciation and stability can be strongly influenced by steric and electronic tuning of the MACHO scaffold. More specifically, a cyclohexyl-derivative, Ru-MACHO\u003csup\u003eCy\u003c/sup\u003e, proved long-term catalyst stability under flow conditions, enabling continuous operation over extended timescales. Translation of the optimised system to a larger reactor configuration afforded sustained syngas production over 84 hours, reaching record turnover numbers for both hydrogen and carbon monoxide. Beyond performance improvements, this work demonstrates that reactor design and catalyst development must be considered together to unlock new operating regimes inaccessible under batch conditions. By aligning renewable methanol-to-syngas reforming with established syngas-demanding processes, this modular flow system provides a scalable strategy for integrating renewable syngas into existing chemical infrastructures.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eSee supplementary Information for further methods.\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData Availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll reported data is available in the supplementary information.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe are deeply grateful to Heraeus Precious Metals GmbH \u0026amp; Co. KG, who supported this study by providing rhodium precursors. We also thank Prof. Dr. Kleber Thiago de Oliveira and Dr. Rodrigo Costa e Silva for the fruitful discussions.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe are grateful for financial support by Villum Fonden (Grant No. 71056, T.S.), Danish National Research Foundation (Grant No. DNRF118, T.S. and DNRF93), the Novo Nordisk Foundation (Grant no. NNF21SA0072700) and Aarhus University. Furthermore, support from the European Union\u0026rsquo;s Horizon 2020 research and innovation program under grant agreement No 862179 and Marie Sklodowska-Curie grant agreement No 859910 is also gratefully acknowledged.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualisation and writing/revising of the original draft were carried out by A.B., G.M.F.B. and T.S. Experiment design and experimental investigations were carried out by A.B., G.M.F.B. and M.G. Funding acquisition was carried out by T.S. All authors reviewed the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eT.S. is co-owner of SyTracks A/S, which commercialises CO tubes.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAnastas, P. T. \u0026amp; Leitner, W. Transform the World through Chemistry. \u003cem\u003eAngew. Chem. Int. Ed. \u003c/em\u003e\u003cstrong\u003e64\u003c/strong\u003e, e202512699 (2025).\u003c/li\u003e\n\u003cli\u003eEuan Casey \u003cem\u003eet al.\u003c/em\u003e Catalysing change: Defossilising the chemical industry \u0026ndash; policy briefing. \u003cem\u003eISBN: 978-1-78252-705-3\u003c/em\u003e Preprint at (2024).\u003c/li\u003e\n\u003cli\u003eUnited Nations Framework Convention on Climate Change. The Paris Agreement. https://unfccc.int/sites/default/files/english_paris_agreement.pdf (2016).\u003c/li\u003e\n\u003cli\u003eWelton, T. \u003cem\u003eet al.\u003c/em\u003e Stockholm Declaration on Chemistry for the Future. \u003cem\u003eRSC Sustain.\u003c/em\u003e \u003cstrong\u003e3\u003c/strong\u003e, 4187\u0026ndash;4189 (2025).\u003c/li\u003e\n\u003cli\u003eLopez, G., Keiner, D., Fasihi, M., Koiranen, T. \u0026amp; Breyer, C. From fossil to green chemicals: sustainable pathways and new carbon feedstocks for the global chemical industry. \u003cem\u003eEnergy Environ. Sci.\u003c/em\u003e \u003cstrong\u003e16\u003c/strong\u003e, 2879\u0026ndash;2909 (2023).\u003c/li\u003e\n\u003cli\u003eHuo, J., Wang, Z., Oberschelp, C., Guill\u0026eacute;n-Gos\u0026aacute;lbez, G. \u0026amp; Hellweg, S. Net-zero transition of the global chemical industry with CO\u003csub\u003e2\u003c/sub\u003e -feedstock by 2050: feasible yet challenging. \u003cem\u003eGreen Chem.\u003c/em\u003e \u003cstrong\u003e25\u003c/strong\u003e, 415\u0026ndash;430 (2023).\u003c/li\u003e\n\u003cli\u003eOlah, G. A. Beyond Oil and Gas: The Methanol Economy. \u003cem\u003eAngew. Chem. Int. Ed.\u003c/em\u003e \u003cstrong\u003e44\u003c/strong\u003e, 2636\u0026ndash;2639 (2005).\u003c/li\u003e\n\u003cli\u003eKang, Seungwoo. \u003cem\u003eInnovation Outlook: Renewable Methanol\u003c/em\u003e. (International Renewable Energy Agency, 2021).\u003c/li\u003e\n\u003cli\u003eSunley, G. J. \u0026amp; Watson, D. J. High productivity methanol carbonylation catalysis using iridium. \u003cem\u003eCatal. Today\u003c/em\u003e \u003cstrong\u003e58\u003c/strong\u003e, 293\u0026ndash;307 (2000).\u003c/li\u003e\n\u003cli\u003eTian, P., Wei, Y., Ye, M. \u0026amp; Liu, Z. Methanol to Olefins (MTO): From Fundamentals to Commercialization. \u003cem\u003eACS Catal.\u003c/em\u003e \u003cstrong\u003e5\u003c/strong\u003e, 1922\u0026ndash;1938 (2015).\u003c/li\u003e\n\u003cli\u003eOlsbye, U. \u003cem\u003eet al.\u003c/em\u003e Conversion of Methanol to Hydrocarbons: How Zeolite Cavity and Pore Size Controls Product Selectivity. \u003cem\u003eAngew. Chem. Int. Ed.\u003c/em\u003e \u003cstrong\u003e51\u003c/strong\u003e, 5810\u0026ndash;5831 (2012).\u003c/li\u003e\n\u003cli\u003eBecka, R., Bajohr, S. \u0026amp; Kolb, T. Review on CO\u003csub\u003e2\u003c/sub\u003e Activation via Catalytic Reverse Water‐Gas Shift Reaction. \u003cem\u003eChem. Ing. Tech.\u003c/em\u003e \u003cstrong\u003e97\u003c/strong\u003e, 860\u0026ndash;881 (2025).\u003c/li\u003e\n\u003cli\u003eChoi, Y. \u003cem\u003eet al.\u003c/em\u003e Copper catalysts for CO\u003csub\u003e2\u003c/sub\u003e hydrogenation to CO through reverse water\u0026ndash;gas shift reaction for e-fuel production: Fundamentals, recent advances, and prospects. \u003cem\u003eChem. Eng. J.\u003c/em\u003e \u003cstrong\u003e492\u003c/strong\u003e, 152283 (2024).\u003c/li\u003e\n\u003cli\u003eKaithal, A., Chatterjee, B., Werl\u0026eacute;, C. \u0026amp; Leitner, W. Acceptorless Dehydrogenation of Methanol to Carbon Monoxide and Hydrogen using Molecular Catalysts. \u003cem\u003eAngew. Chem. Int. Ed.\u003c/em\u003e \u003cstrong\u003e60\u003c/strong\u003e, 26500\u0026ndash;26505 (2021).\u003c/li\u003e\n\u003cli\u003eYang, L. \u003cem\u003eet al.\u003c/em\u003e Mechanistic Insight into Acceptorless Dehydrogenation of Methanol to Syngas Catalyzed by MACHO-Type Ruthenium and Manganese Complexes: A DFT Study. \u003cem\u003eInorg. Chem.\u003c/em\u003e \u003cstrong\u003e62\u003c/strong\u003e, 19516\u0026ndash;19526 (2023).\u003c/li\u003e\n\u003cli\u003eLiu, J. \u003cem\u003eet al.\u003c/em\u003e Outer-Sphere CO Release Mechanism in the Methanol-to-Syngas Reaction Catalyzed by a Ru-PNP Pincer Complex. \u003cem\u003eACS Catal.\u003c/em\u003e \u003cstrong\u003e15\u003c/strong\u003e, 5113\u0026ndash;5122 (2025).\u003c/li\u003e\n\u003cli\u003eBonde, A. \u003cem\u003eet al.\u003c/em\u003e Integrating hydroformylations with methanol-to-syngas reforming. \u003cem\u003eChem\u003c/em\u003e \u003cstrong\u003e11\u003c/strong\u003e, 102396 (2025).\u003c/li\u003e\n\u003cli\u003eStahl, S., Vossen, J. T., Popp, S., Leitner, W. \u0026amp; Vorholt, A. J. Methanolation of Olefins: Low‐Pressure Synthesis of Alcohols by the Formal Addition of Methanol to Olefins. \u003cem\u003eAngew. Chem. Int. Ed.\u003c/em\u003e \u003cstrong\u003e64\u003c/strong\u003e, e202418984 (2025).\u003c/li\u003e\n\u003cli\u003eTindall, D. J. \u003cem\u003eet al.\u003c/em\u003e Ru\u003csup\u003e0\u003c/sup\u003e or Ru\u003csup\u003eII\u003c/sup\u003e : A Study on Stabilizing the \u0026ldquo;Activated\u0026rdquo; Form of Ru-PNP Complexes with Additional Phosphine Ligands in Alcohol Dehydrogenation and Ester Hydrogenation. \u003cem\u003eInorg. Chem.\u003c/em\u003e \u003cstrong\u003e59\u003c/strong\u003e, 5099\u0026ndash;5115 (2020).\u003c/li\u003e\n\u003cli\u003eAnaby, A. \u003cem\u003eet al.\u003c/em\u003e Study of Precatalyst Degradation Leading to the Discovery of a New Ru \u003csup\u003e0\u003c/sup\u003e Precatalyst for Hydrogenation and Dehydrogenation. \u003cem\u003eOrganometallics\u003c/em\u003e \u003cstrong\u003e37\u003c/strong\u003e, 2193\u0026ndash;2201 (2018).\u003c/li\u003e\n\u003cli\u003eFriedrich, A., Drees, M., K\u0026auml;ss, M., Herdtweck, E. \u0026amp; Schneider, S. Ruthenium Complexes with Cooperative PNP-Pincer Amine, Amido, Imine, and Enamido Ligands: Facile Ligand Backbone Functionalization Processes. \u003cem\u003eInorg. Chem.\u003c/em\u003e \u003cstrong\u003e49\u003c/strong\u003e, 5482\u0026ndash;5494 (2010).\u003c/li\u003e\n\u003cli\u003eK\u0026auml;\u0026szlig;, M., Friedrich, A., Drees, M. \u0026amp; Schneider, S. Ruthenium Complexes with Cooperative PNP Ligands: Bifunctional Catalysts for the Dehydrogenation of Ammonia\u0026ndash;Borane. \u003cem\u003eAngew. Chem. Int. Ed.\u003c/em\u003e \u003cstrong\u003e48\u003c/strong\u003e, 905\u0026ndash;907 (2009).\u003c/li\u003e\n\u003cli\u003eNguyen, D. H. \u003cem\u003eet al.\u003c/em\u003e Deeper Mechanistic Insight into Ru Pincer-Mediated Acceptorless Dehydrogenative Coupling of Alcohols: Exchanges, Intermediates, and Deactivation Species. \u003cem\u003eACS Catal.\u003c/em\u003e \u003cstrong\u003e8\u003c/strong\u003e, 4719\u0026ndash;4734 (2018).\u003c/li\u003e\n\u003cli\u003eZhang, L. \u003cem\u003eet al.\u003c/em\u003e Catalytic Conversion of Alcohols into Carboxylic Acid Salts in Water: Scope, Recycling, and Mechanistic Insights. \u003cem\u003eChemSusChem\u003c/em\u003e \u003cstrong\u003e9\u003c/strong\u003e, 1413\u0026ndash;1423 (2016).\u003c/li\u003e\n\u003cli\u003eOgata, O., Nara, H., Fujiwhara, M., Matsumura, K. \u0026amp; Kayaki, Y. \u003cem\u003eN\u003c/em\u003e -Monomethylation of Aromatic Amines with Methanol via PNP-Pincer Ru Catalysts. \u003cem\u003eOrg. Lett.\u003c/em\u003e \u003cstrong\u003e20\u003c/strong\u003e, 3866\u0026ndash;3870 (2018).\u003c/li\u003e\n\u003cli\u003eKar, S. \u003cem\u003eet al.\u003c/em\u003e Mechanistic Insights into Ruthenium-Pincer-Catalyzed Amine-Assisted Homogeneous Hydrogenation of CO \u003csub\u003e2\u003c/sub\u003e to Methanol. \u003cem\u003eJ. Am. Chem. Soc.\u003c/em\u003e \u003cstrong\u003e141\u003c/strong\u003e, 3160\u0026ndash;3170 (2019).\u003c/li\u003e\n\u003cli\u003eAlberico, E. \u003cem\u003eet al.\u003c/em\u003e Unravelling the Mechanism of Basic Aqueous Methanol Dehydrogenation Catalyzed by Ru\u0026ndash;PNP Pincer Complexes. \u003cem\u003eJ. Am. Chem. Soc.\u003c/em\u003e \u003cstrong\u003e138\u003c/strong\u003e, 14890\u0026ndash;14904 (2016).\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"nature-portfolio","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Nature Portfolio","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"ejp","reportingPortfolio":"","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-9102906/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9102906/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Carbon-based feedstocks, including oil, coal, and natural gas, are essential raw materials for the chemical industry. This makes the transition away from fossil resources challenging compared to energy and transportation sectors. Renewable methanol has emerged as a promising liquid C1 platform that could provide a drop-in route to synthesis gas (syngas), a central intermediate in large-scale chemical production. However, homogeneous methanol-to-syngas reforming is typically performed in closed batch reactors, where accumulation of gaseous products rapidly suppresses catalytic turnover. Here we report a continuous flow system for homogeneous methanol-to-syngas reforming using Ru-MACHO-based catalysts that overcomes these limitations through continuous separation of gaseous products from the catalytic phase. Systematic optimisation using a design-of-experiments strategy identified the key operational parameters governing productivity, while ligand design enabled improved catalyst stability under flow conditions. The resulting system enables sustained syngas generation over extended operation and delivers substantially enhanced catalytic performance relative to batch operation. These findings demonstrate how combining reactor operation with molecular catalyst design can unlock new operating regimes for equilibrium-limited homogeneous catalytic transformations.","manuscriptTitle":"Enabling high-turnover methanol-to-syngas reforming","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-31 08:30:11","doi":"10.21203/rs.3.rs-9102906/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"nature-communications","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"NCOMMS","sideBox":"Learn more about [Nature Communications](http://www.nature.com/ncomms/)","snPcode":"","submissionUrl":"https://mts-ncomms.nature.com/","title":"Nature Communications","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature Communications","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"bf689040-c8e9-457f-96d3-36320be3cb6f","owner":[],"postedDate":"March 31st, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":64378627,"name":"Physical sciences/Chemistry/Catalysis"},{"id":64378628,"name":"Physical sciences/Chemistry/Green chemistry/Sustainability"},{"id":64378629,"name":"Physical sciences/Chemistry/Catalysis/Homogeneous catalysis"},{"id":64378630,"name":"Physical sciences/Chemistry/Chemical synthesis/Flow chemistry"}],"tags":[],"updatedAt":"2026-04-20T09:17:29+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-31 08:30:11","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9102906","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9102906","identity":"rs-9102906","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}