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Related Concept Videos

Keto–Enol Tautomerism: Mechanism01:14

Keto–Enol Tautomerism: Mechanism

8.4K
The keto and enol forms are known as tautomers and they constantly interconvert (or tautomerize) between the two forms under acid or base catalyzed conditions. Both the reactions involve the same steps—protonation and deprotonation— although in the reverse order.
8.4K
Reactivity of Enols01:18

Reactivity of Enols

4.5K
Enols are a class of compounds where a hydroxyl group is attached to a carbon–carbon double bond, which implies that it is a vinyl alcohol. A carbonyl compound with an α hydrogen undergoes keto–enol tautomerism and remains in equilibrium with its tautomer, the enol form. Usually, the keto tautomer is present in a higher concentration than the enol tautomer due to the higher bond energy of C=O compared to C=C. Moreover, the direction of the keto–enol equilibrium is...
4.5K
Regioselective Formation of Enolates01:33

Regioselective Formation of Enolates

3.7K
As depicted in the figure below, the unsymmetrical ketones can form two possible enolates:  less substituted or more substituted enolates. Usually, the thermodynamic enolates are formed from the more substituted α-carbon atom, while the kinetic enolates are formed faster by deprotonation from the less substituted position. The thermodynamic enolates have lower energy, so they are  more stable. But the energy required to form kinetic enolates is less.
3.7K
Types of Enols and Enolates01:19

Types of Enols and Enolates

4.0K
Aldehydes and ketones form enols, although only about 1% of the enol is present at the equilibrium for simple monocarbonyl compounds. The enol form is undetectable for acetaldehyde, present as only 1.5 × 10−4 % of acetone, and present as only 1.2% of cyclohexanone. Two kinds of regioisomeric enols are possible for unsymmetrical ketones, and their net composition is 1% at equilibrium. This instability is due to the lower bond energy of C=C than the C=O group. The additional...
4.0K
Solvating Effects02:12

Solvating Effects

9.2K
An understanding of the solvating effect helps rationalize the relation between solvation and acidity of the compound. In addition, this also explains the relative stability of conjugate bases for compounds with different pKa values. This lesson details, in-depth, the principle of solvating effects. The strength of an acid and the stability of its corresponding conjugate base are determined using pKa values. This observed relationship is a consequence of solvation, which is the interaction...
9.2K
Alkylation of β-Ketoester Enolates: Acetoacetic Ester Synthesis01:07

Alkylation of β-Ketoester Enolates: Acetoacetic Ester Synthesis

4.9K
Acetoacetic ester synthesis is a method to obtain ketones from alkyl halides and β-keto esters. The reaction occurs in the presence of an alkoxide base that abstracts the acidic proton of the β-keto esters. The step results in an enolate ion which is doubly stabilized. The enolate then reacts with an alkyl halide via the SN2 process to produce an alkylated ester intermediate with a new C–C bond. The hydrolysis of the intermediate, followed by acidification, results in an...
4.9K

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Unraveling Entropic Rate Acceleration Induced by Solvent Dynamics in Membrane Enzymes
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Benchmarking Continuum Solvent Models for Keto-Enol Tautomerizations.

Billy W McCann1, Stuart McFarland1, Orlando Acevedo1

  • 1Department of Chemistry and Biochemistry, Auburn University, Auburn, Alabama 36849, United States.

The Journal of Physical Chemistry. A
|July 24, 2015
PubMed
Summary

Accurate quantum mechanical methods like G4 and M06/6-31+G(d,p) predict tautomerization free energies in gas and solution phases. G4/PCM with the UA0 cavity is the most accurate for diverse tautomer pairs across solvents.

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Area of Science:

  • Computational Chemistry
  • Quantum Mechanics
  • Physical Organic Chemistry

Background:

  • Accurate prediction of tautomerization free energies (ΔGT) is crucial for understanding chemical reactivity.
  • Previous studies have evaluated various quantum mechanical (QM) methods for gas-phase predictions, but comprehensive benchmarking in solution is less explored.

Purpose of the Study:

  • To benchmark the accuracy of 17 QM methods and 8 basis sets for gas-phase tautomerization free energies.
  • To compute and evaluate solution-phase ΔGT values using accurate QM methods and continuum solvation models.
  • To investigate the mechanism of base-catalyzed keto-enol interconversion.

Main Methods:

  • Gas-phase ΔGT calculations for seven keto-enol tautomer pairs using 17 QM methods and 8 basis sets.
  • Solution-phase ΔGT calculations for 23 tautomer pairs using G4 and M06/6-31+G(d,p) with PCM, CPCM, and SMD solvation models.
  • Calculation of free energies of activation (ΔG‡) for 2-nitrocyclohexanone enolization using M06/6-31+G(d,p) with CPCM and SMD.

Main Results:

  • G4 and M06/6-31+G(d,p) demonstrated the highest accuracy for gas-phase ΔGT predictions (MAE 0.95 and 0.71 kcal/mol, respectively).
  • Continuum solvation models yielded similar MAEs for solution-phase ΔGT (∼1.6-2.0 kcal/mol).
  • G4/PCM with the UA0 cavity showed the best overall accuracy for diverse tautomer pairs in various solvents.
  • M06/6-31+G(d,p) accurately reproduced activation free energies for 2-nitrocyclohexanone enolization.
  • Calculations suggest a stepwise mechanism for 2-nitrocyclohexanone enolization across all tested solvents.

Conclusions:

  • The G4 and M06/6-31+G(d,p) methods are highly reliable for predicting tautomerization free energies.
  • The G4/PCM (UA0) combination provides the most accurate results for solution-phase tautomerization.
  • The mechanism of 2-nitrocyclohexanone enolization appears to be consistently stepwise, regardless of solvent polarity.