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Acid‐Catalyzed Nucleophilic Aromatic Substitution: Experimental and Theoretical Exploration of a Multistep Mechanism
Author(s) -
Jacobsson Mårten,
Oxgaard Jonas,
Abrahamsson CarlOlof,
Norrby PerOla,
Goddard William A.,
Ellervik Ulf
Publication year - 2008
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200701590
Subject(s) - chemistry , cationic polymerization , protonation , nucleophile , toluene , nucleophilic substitution , catalysis , reaction mechanism , substitution reaction , acid catalysis , medicinal chemistry , photochemistry , transition state , computational chemistry , ion , polymer chemistry , organic chemistry
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 ( p TsOH) 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 ( p TsOH). Experimentally determined activation parameters are similar to the calculated values (Δ H exp ≠ =105±9, Δ H calcd ≠ =118 kJ mol −1 ; Δ G exp ≠ =112±18, Δ G calcd ≠ =142 kJ mol −1 ).