Rapid multistep kinetic model generation from transient flow data

Hone, Christopher A.; Holmes, Nicholas P.; Akien, Geoffrey R.; Bourne, Richard A.; Muller, Frans L.

doi:10.1039/c6re00109b

Cited by 86 publications

(84 citation statements)

References 33 publications

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“…General methodologies and applications of flow chemistry combined with heterogeneous catalysis are addressed in a variety of recent reviews, covering aspects from materials science and microreactor types to process safety and intensification . Based on these principles, advanced techniques for continuous‐flow kinetics studies were introduced, which use transient flow or temperature profiles to investigate the kinetics of chemical reactions . Thereby, the reaction progress was investigated on microreactors operating under non‐steady‐state conditions in order to eliminate the time necessary to reach steady‐state operation and, consequently, to reduce the amount of consumed starting material, experiment time, and produced waste.…”

Section: Resultsmentioning

confidence: 99%

Kinetics Studies on a Multicomponent Knoevenagel−Michael Domino Reaction by an Automated Flow Reactor

Haas

Tallarek

2019

ChemistryOpen

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The optimization of complex chemical reaction systems is often a troublesome and time‐consuming process. The application of modern technologies, including automated reactors and analytics, opens the avenue for generating large data sets on chemical reaction processes in a short period of time. In this work, an automated flow reactor is used to present detailed kinetics and mechanistic studies about an amine‐catalyzed Knoevenagel−Michael domino reaction to yield tetrahydrochromene derivatives. High‐performance monoliths as catalyst supports and online coupled HPLC analysis allow for time‐efficient data generation. We show that the two‐step multicomponent domino reaction does not follow the kinetics of consecutive reaction steps proceeding independently from each other. Instead, the starting materials of both individual reactions compete for the active sites on the heterogeneous catalyst, which lowers the rate constants of both steps. This knowledge was used to implement a more efficient experimental setup which increased the turnover numbers of the catalyst, without adjusting common reaction parameters like temperature, reaction time, and concentrations.

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Section: Resultsmentioning

confidence: 99%

Kinetics Studies on a Multicomponent Knoevenagel−Michael Domino Reaction by an Automated Flow Reactor

Haas

Tallarek

2019

ChemistryOpen

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“…They were able to gather multistep kinetic information about a nucleophilic aromatic substitution (Scheme 15A) [117] and showed self-optimization of different reactions with their systems (Scheme 15B and C). [118] …”

Section: One Machine – Many Small Moleculesmentioning

confidence: 99%

The Molecular Industrial Revolution: Automated Synthesis of Small Molecules

2018

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The eighteenth and nineteenth centuries marked a sweeping transition from manual to automated manufacturing on the macroscopic scale. This enabled an unmatched period of human innovation that helped drive the Industrial Revolution. The impact on society was transformative, ultimately yielding substantial improvements in living conditions and lifespan in many parts of the world. During the same time period, the first manual syntheses of organic molecules was achieved. Now, two centuries later, we are poised for an analogous transition from highly customized crafting of specific molecular targets by hand to the increasingly general and automated assembly of many different types of molecules with the push of a button. Automation of customized small molecule synthesis pathways is already enabling safer, more reproducible, and readily scalable production of specific targets, and general machines now exist for the synthesis of a wide range of different peptides, oligonucleotides, and oligosaccharides. Creating general machines that are similarly capable of making many different types of small molecules on-demand, akin to that which has been achieved on the macroscopic scale with 3D printers, has proven to be substantially more challenging. Yet important progress is being made toward this potentially transformative objective with two complementary approaches: (1) automation of customized synthesis routes to different targets via machines that enable use of many different reactions and starting materials, and (2) automation of generalized platforms that make many different targets using common coupling chemistry and building blocks. Continued progress in these exciting directions has the potential to shift the bottleneck in molecular innovation from synthesis to imagination, and thereby help drive a new industrial revolution on the molecular scale.

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“…39 Specifically for our microreactor system, the dispersion has been calculated to only introduce a very small deviation from plug flow reactor conditions. 31,36,39,40 In order to accurately observe a range of residence times within one experiment, from the derivation previously reported, a linear ramp in residence time can be generated from an exponential change in flowrate.…”

Section: Methodsmentioning

confidence: 99%

“…35 Hone et al then applied this method to a multistep S N Ar reaction in order to demonstrate its robustness for more complex mechanisms and the effect of dispersion in these systems. 36 This work introduces a new approach that builds upon previously reported studies, resulting in a more efficient method for reaction kinetics. The approach, outlined in Fig.…”

Section: Introductionmentioning

confidence: 99%

“…[29][30][31][32] Recent studies have shown that transient flow data could be used to quickly generate kinetic data. [33][34][35][36] Mozharov used the transient data generated from a step change in flow to scan different reaction times and fit kinetic data collected with inline Raman spectroscopy. 33 However it was concluded that the method was limited since the procedure to extract kinetics was based on estimating when the transient flow started and stopped.…”

Section: Introductionmentioning

confidence: 99%

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Efficient kinetic experiments in continuous flow microreactors

Aroh

Jensen

2018

React. Chem. Eng.

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Flow chemistry is an enabling technology that can offer an automated and robust approach for the generation of reaction kinetics data. Recent studies have taken advantage of transient flows to quickly generate concentration profiles with various online analytical tools. In this work, we demonstrate an improved method where temperature and flow are transient throughout the reaction. It was observed that only two orthogonal temperature ramp experiments under the same transient flow condition were sufficient to characterize a Paal-Knorr (one step bimolecular) reaction within our chosen reaction space. This method further shortens the time and decreases the materials needed to collect sufficient kinetic data and provides a framework with which more complex kinetic studies could be performed.

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Rapid multistep kinetic model generation from transient flow data

Abstract: SNAr reaction profiles were generated using an automated reactor, collected in less than 3 hours, and allowed accurate estimation of kinetic parameters.

Cited by 86 publications

References 33 publications

Kinetics Studies on a Multicomponent Knoevenagel−Michael Domino Reaction by an Automated Flow Reactor

Kinetics Studies on a Multicomponent Knoevenagel−Michael Domino Reaction by an Automated Flow Reactor

The Molecular Industrial Revolution: Automated Synthesis of Small Molecules

Efficient kinetic experiments in continuous flow microreactors

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