Acid-catalyzed nucleophilic aromatic substitution: experimental and theoretical exploration of a multistep mechanism.
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 (Delta H exp not equal =105+/-9, Delta H calcd not equal =118 kJ mol(-1); Delta G exp not equal =112+/-18, Delta G calcd not equal =142 kJ mol(-1)).
Jacobsson
Mårten
M
Organic Chemistry, Lund University, PO Box 124, 22100 Lund, Sweden.
Oxgaard
Jonas
J
Abrahamsson
Carl-Olof
CO
Norrby
Per-Ola
PO
Goddard
William A
WA
Ellervik
Ulf
U
D000143:Acids / Q000737:chemistry*; D002384:Catalysis; D007700:Kinetics; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure
D000143:Acids