Statistical thermodynamics unveils how ions influence an aqueous Diels-Alder reaction

Joshua Elias Samuel James Reid, Pedro H. G. Aquino, Adam J. Walker, Peter Borislavov Karadakov, Seishi Shimizu

Research output: Contribution to journalArticlepeer-review


The kinetics of Diels-Alder (DA) reactions in water has been known to be altered by salts for a long time. Yet the question how salts influence the reaction rate, either as rate-enhancing or rate-reducing additives, has so far remained unresolved. Conflicting hypotheses involve (i) indirect salt contributions through the modulation of internal pressure and (ii) making (or breaking) of the so-called “water-structure” by salts that strengthen (or weaken) the hydrophobic effect. In contrast to the qualitative nature of these hypotheses, here we answer this question quantitatively through a combination of transition state theory and fluctuation adsorption-solvation theory (FAST) using the DA reaction between anthracene-9-carbinol and N-ethylmaleimide as an example. We show that rate enhancement is driven by the salting out of the hydrophobic reactant, while rate-enhancing salts exhibit stronger affinity to the transition state.

Original languageEnglish
Pages (from-to)1538-1544
Number of pages7
Issue number11
Early online date23 Apr 2019
Publication statusPublished - 4 Jun 2019

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  • Diels-Alder reaction
  • Kirkwood-Buff theory
  • salts
  • statistical thermodynamics
  • water

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