Ionic liquid effects on nucleophilic aromatic substitution reactions from QM/MM simulations

Caley Allen, Billy W. McCann, Orlando Acevedo

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Nucleophilic aromatic substitution (SNAr) reactions are particularly sensitive to medium effects and have been reported to benefit from ionic liquids. The SNAr reaction between cyclic secondary amines (i.e., piperidine, pyrrolidine, and morpholine) and the 2-L-5-nitrothiophene (para-like) and 2-L-3-nitrothiophene (ortho-like) isomers, where L = bromo, methoxy, phenoxy, and 4-nitrophenoxy, has been computationally investigated in 1-butyl-3-methylimidazolium tetrafluoroborate and hexafluorophosphate [BMIM][BF4] and [BMIM][PF6], respectively. QM/MM Monte Carlo simulations utilizing free-energy perturbation theory were used to characterize the solute-solvent interactions over the addition-elimination reaction pathway. Energetic and structural analyses determined that the improved SNAr reactivity in [BMIM][BF4] and [BMIM][PF6] can be attributed to (1) an enhanced nucleophilicity of the cyclic amines in the ionic liquids with an order of Pyr ≥ Pip > Mor, (2) beneficial +- interactions between the BMIM cations and the aromatic rings present on the substrate that enhanced coplanarity between the thiophene ring and the aromatic substituents, resulting in a larger positive charge on the reacting ipso carbon, and (3) a highly ordered ionic liquid clathrate formation that, despite an entropy penalty, provided reduced activation free-energy barriers derived from an increasing number of solvent ions favorably interacting with the emerging charge separation at the rate-limiting addition step.

Original languageEnglish (US)
Pages (from-to)743-752
Number of pages10
JournalJournal of Physical Chemistry B
Volume119
Issue number3
DOIs
StatePublished - Jan 22 2015
Externally publishedYes

Fingerprint

Ionic Liquids
Ionic liquids
Substitution reactions
substitutes
Free energy
Amines
amines
liquids
free energy
coplanarity
Thiophenes
piperidine
simulation
rings
Energy barriers
clathrates
Thiophene
polarization (charge separation)
thiophenes
penalties

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Materials Chemistry
  • Surfaces, Coatings and Films

Cite this

Ionic liquid effects on nucleophilic aromatic substitution reactions from QM/MM simulations. / Allen, Caley; McCann, Billy W.; Acevedo, Orlando.

In: Journal of Physical Chemistry B, Vol. 119, No. 3, 22.01.2015, p. 743-752.

Research output: Contribution to journalArticle

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