Base-Catalyzed Dehydration of 3‑Substituted Benzene cis-1,2-Dihydrodiols: Stabilization of a Cyclohexadienide Anion Intermediate by Negative Aromatic Hyperconjugation

• Published in: Journal of the American Chemical Society Vol. 134; no. 34; pp. 14056 - 14069
• Main Authors: Kudavalli, Jaya Satyanarayana, Rao, S. Nagaraja, Bean, David E, Sharma, Narain D, Boyd, Derek R, Fowler, Patrick W, Gronert, Scott, Kamerlin, Shina Caroline Lynn, Keeffe, James R, More O’Ferrall, Rory A
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 29.08.2012
• Subjects: anions; Anions - chemistry; benzene; Benzene - chemistry; Catalysis; cations; Cyclohexenes - chemistry; heat production; hydrogen; isotopes; Kinetics; phenol; Phenols - chemistry; solvents; Water - chemistry
• ISSN: 0002-7863; 1520-5126; 1520-5126
• DOI: 10.1021/ja304366j

Evidence that a 1,2-dihydroxycyclohexadienide anion is stabilized by aromatic “negative hyperconjugation” is described. It complements an earlier inference of “positive” hyperconjugative aromaticity for the cyclohexadienyl cation. The anion is a reactive intermediate in the dehydration of benzene cis-1,2-dihydrodiol to phenol. Rate constants for 3-substituted benzene cis-dihydrodiols are correlated by σ– values with ρ = 3.2. Solvent isotope effects for the reactions are k H2O/k D2O = 1.2–1.8. These measurements are consistent with reaction via a carbanion intermediate or a concerted reaction with a “carbanion-like” transition state. These and other experimental results confirm that the reaction proceeds by a stepwise mechanism, with a change in rate-determining step from proton transfer to the loss of hydroxide ion from the intermediate. Hydrogen isotope exchange accompanying dehydration of the parent benzene cis-1,2-dihydrodiol was not found, and thus, the proton transfer step is subject to internal return. A rate constant of ∼1011 s–1, corresponding to rotational relaxation of the aqueous solvent, is assigned to loss of hydroxide ion from the intermediate. The rate constant for internal return therefore falls in the range 1011–1012 s–1. From these limiting values and the measured rate constant for hydroxide-catalyzed dehydration, a pK a of 30.8 ± 0.5 was determined for formation of the anion. Although loss of hydroxide ion is hugely exothermic, a concerted reaction is not enforced by the instability of the intermediate. Stabilization by negative hyperconjugation is proposed for 1,2-dihydroxycyclohexadienide and similar anions, and this proposal is supported by additional experimental evidence and by computational results, including evidence for a diatropic (“aromatic”) ring current in 3,3-difluorocyclohexadienyl anion.