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

Abstract

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.

The Element Effect Revisited: Factors Determining Leaving Group Ability in Activated Nucleophilic Aromatic Substitution Reactions

“…In Meisenheimer complexes such hyperconjugation, always involving pseudoaxial C–F bonds, will result in stabilization by providing a measure of aromaticity, that is, “hyperaromaticity” to the anion. 30 In fact the longest C–F bond in Table 5 is found for addition of fluoride to C6 of 2,4-dinitrophenyl fluoride. That position is the only position not activated by ortho - or para -nitro groups.…”

“…In fact, they argue that the anomeric interaction is compromised by negative hyperconjugation. We suggest that the superior negative hyperconjugative ability of fluoride compared with chloride and bromide provides additional “hyperaromatic” stabilization of the fluoro transition state, 30 illustrated for example by the no-bond resonance structure depicted below.…”

Concerted or Stepwise: How Much Do Free-Energy Landscapes Tell Us about the Mechanisms of Elimination Reactions?

“…Recently, More-O’Ferrall provided the first evidence that, for benzene cis -1,2-dihydrodiols, this reaction also occurs under base catalysis at room temperature with aqueous sodium hydroxide. 5 Conceptually, this is a very interesting system because the generation of an aromatic system provides a potent thermodynamic driving force that can overcome the disadvantages of a very poor leaving group. Moreover, the experiments suggest an unusual shift in mechanism and kinetic isotope effects with the addition of electron-withdrawing groups.…”

Reactivity in the nucleophilic aromatic substitution reactions of pyridinium ions

“…For the 2-cyano, 4-cyano, and 2-fluoro versions of I-2 the heterocyclic rings are puckered, the C-L bonds are slightly longer than normal length for sp 3 carbon, especially the C-F bond, and, importantly, the N-C2 distances within the heterocycle are longer (1.460, 1.506, and 1.492 Å, respectively) than those in the original aromatic substrates (1.352, 1.340, and 1.329 Å, respectively). The latter lengths reflect the degree of aromaticity in the ring, and tell us that in these three cases I-2 is an ordinary molecule, not aromatic, albeit with some “hyperaromatic” character, particularly for L = F. 26 In contrast I-2 for the 2-chloro and 2-bromo versions show flat heterocyclic rings, very long C-L bonds (2.949 and 3.045 Å, respectively) and short N-C2 bonds within the heterocycle: 1.365 and 1.367 Å, respectively; compare with 1.342 and 1.343 Å for the substrates. In fact for L − = chloride and bromide I-2 can be considered an ion-pair complex between product and L − , formed by departure of L − from I-2 , and not a stable covalent neutral.…”