‘One-Pot’ kinetic profiling of SNAr Reactions via Sequential Addition Kinetic Elucidation (SAKE)
File(s)
Accepted version
Author(s)
Dalland, Daniel
Hii, King Kuok Mimi
Atkins, Alexander P
Schrecker, Linden
Type
Journal Article
Abstract
Efficient acquisition of high-quality kinetic data under synthetically relevant conditions remains a major bottleneck in reaction development and process optimisation. Here, we introduce Sequential Addition Kinetic Elucidation (SAKE), a one-pot methodology that generates multiple kinetic datasets within a single experiment through staged reagent dosing and continuous in situ monitoring. This approach minimises inter-experimental variability while maximising data density, enabling robust extraction of global rate laws using automated analysis tools. The SAKE protocol is demonstrated using nucleophilic aromatic substitution (SNAr) reactions between aryl phenyl ethers and secondary amines, a system featuring competing uncatalysed and base-catalysed pathways. Integration with Auto-VTNA and microkinetic modelling enables quantitative determination of rate parameters, including pathway-specific rate constants and reversible inhibition by phenol. By systematically varying temperature, electrophile electronics, amine basicity, and solvent, quantitative relationships between reaction conditions and kinetic behaviour, including predictive correlations with solvent descriptors, can be established. Compared to conventional kinetic workflows requiring multiple independent experiments, SAKE significantly reduces experimental effort while providing mechanistically rich datasets under process-relevant conditions. This methodology offers a general framework for accelerating kinetic analysis, with potential applications in reaction optimisation, solvent selection, and data-driven process development.
Date Issued
2026-08-26
Date Acceptance
2026-08-21
Citation
Reaction Chemistry and Engineering, 2026
ISSN
2058-9883
Publisher
Royal Society of Chemistry
Journal / Book Title
Reaction Chemistry and Engineering
Copyright Statement
© 2026 The Author(s). Published by the Royal Society of Chemistry This article is licensed under a Creative Commons Attribution 4.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.
License URL
Publication Status
Published online
Date Publish Online
2026-08-26