Solvent effects and mechanism for a nucleophilic aromatic substitution from QM/MM simulations

Org Lett. 2004 Aug 19;6(17):2881-4. doi: 10.1021/ol049121k.

Abstract

The nucleophilic aromatic substitution (SNAr) reaction between azide ion and 4-fluoronitrobenzene has been investigated using QM/MM and DFT/PCM calculations in protic and dipolar aprotic solvents. The effects of solvation on the transition structures, the intermediate Meisenheimer complex, and the rate of reaction are elucidated. The large rate increases in proceeding from protic to dipolar aprotic solvents are only reproduced by the QM/MM methodology.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Azides / chemistry*
  • Chemical Phenomena
  • Chemistry, Physical
  • Computer Simulation
  • Molecular Structure
  • Nitrobenzenes / chemistry*
  • Solvents
  • Thermodynamics

Substances

  • Azides
  • Nitrobenzenes
  • Solvents