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Acid-Catalyzed Nucleophilic Aromatic Substitution: Experimental and Theoretical Exploration of a Multistep Mechanism.

Jacobsson, Mårten LU ; Oxgaard, Jonas; Abrahamsson, Carl-Olof; Norrby, Per-Ola; Goddard, William A and Ellervik, Ulf LU (2008) In Chemistry: A European Journal 14(13). p.3954-3960
Abstract
The mechanism for the acid-mediated substitution of a phenolic hydroxyl group with a sulfur nucleophile has been investigated by a combination of experimental and theoretical methods. We conclude that the mechanism is distinctively different in nonpolar solvents (i.e., toluene) compared with polar solvents. The cationic mechanism, proposed for the reaction in polar solvents, is not feasible and the reaction instead proceeds through a multistep mechanism in which the acid (pTsOH) mediates the proton shuffling. From DFT calculations, we found a rate-determining transition state with protonation of the hydroxyl group to generate free water and a tight ion pair between a cationic protonated naphthalene species and a tosylate anion. Kinetic... (More)
The mechanism for the acid-mediated substitution of a phenolic hydroxyl group with a sulfur nucleophile has been investigated by a combination of experimental and theoretical methods. We conclude that the mechanism is distinctively different in nonpolar solvents (i.e., toluene) compared with polar solvents. The cationic mechanism, proposed for the reaction in polar solvents, is not feasible and the reaction instead proceeds through a multistep mechanism in which the acid (pTsOH) mediates the proton shuffling. From DFT calculations, we found a rate-determining transition state with protonation of the hydroxyl group to generate free water and a tight ion pair between a cationic protonated naphthalene species and a tosylate anion. Kinetic experiments support this mechanism and show that, at moderate concentrations, the reaction is first order with respect to 2-naphthol, n-propanethiol, and p-toluenesulfonic acid (pTsOH). Experimentally determined activation parameters are similar to the calculated values (DeltaH(exp) ( not equal)=105+/-9, DeltaH(calcd) ( not equal)=118 kJ mol(-1); DeltaG(exp) ( not equal)=112+/-18, DeltaG(calcd) ( not equal)=142 kJ mol(-1)). (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
aromatic substitution, density functional calculations, kinetics, nucleophilic substitution, reaction mechanisms
in
Chemistry: A European Journal
volume
14
issue
13
pages
3954 - 3960
publisher
John Wiley & Sons
external identifiers
  • pmid:18351696
  • wos:000255703000015
  • scopus:47749086256
ISSN
1521-3765
DOI
10.1002/chem.200701590
language
English
LU publication?
yes
id
697d29dd-1807-4919-9834-cd509ef2438b (old id 1052337)
date added to LUP
2008-05-23 09:44:32
date last changed
2017-07-02 03:49:36
@article{697d29dd-1807-4919-9834-cd509ef2438b,
  abstract     = {The mechanism for the acid-mediated substitution of a phenolic hydroxyl group with a sulfur nucleophile has been investigated by a combination of experimental and theoretical methods. We conclude that the mechanism is distinctively different in nonpolar solvents (i.e., toluene) compared with polar solvents. The cationic mechanism, proposed for the reaction in polar solvents, is not feasible and the reaction instead proceeds through a multistep mechanism in which the acid (pTsOH) mediates the proton shuffling. From DFT calculations, we found a rate-determining transition state with protonation of the hydroxyl group to generate free water and a tight ion pair between a cationic protonated naphthalene species and a tosylate anion. Kinetic experiments support this mechanism and show that, at moderate concentrations, the reaction is first order with respect to 2-naphthol, n-propanethiol, and p-toluenesulfonic acid (pTsOH). Experimentally determined activation parameters are similar to the calculated values (DeltaH(exp) ( not equal)=105+/-9, DeltaH(calcd) ( not equal)=118 kJ mol(-1); DeltaG(exp) ( not equal)=112+/-18, DeltaG(calcd) ( not equal)=142 kJ mol(-1)).},
  author       = {Jacobsson, Mårten and Oxgaard, Jonas and Abrahamsson, Carl-Olof and Norrby, Per-Ola and Goddard, William A and Ellervik, Ulf},
  issn         = {1521-3765},
  keyword      = {aromatic substitution,density functional calculations,kinetics,nucleophilic substitution,reaction mechanisms},
  language     = {eng},
  number       = {13},
  pages        = {3954--3960},
  publisher    = {John Wiley & Sons},
  series       = {Chemistry: A European Journal},
  title        = {Acid-Catalyzed Nucleophilic Aromatic Substitution: Experimental and Theoretical Exploration of a Multistep Mechanism.},
  url          = {http://dx.doi.org/10.1002/chem.200701590},
  volume       = {14},
  year         = {2008},
}