Computational investigations of carbonyl reactions: Comparison between nucleophilic addition versus enolate formation in the reaction of acetaldehyde with hydroxide ion

The induction of strain in carbocycles, thereby increasing the amount of s-character in the C−H bonds and the acidity of these protons, has been probed with regard to its effect on the rate constants for the enolization of cyclobutanone. The second-order rate constants for the general base-catalyzed enolization of cyclobutanone have been determined for a series of 3-substituted quinuclidine buffers in D2O at 25 °C, I = 1.0 M (KCl). The rate constants for enolization were determined by following the extent of deuterium incorporation (up to ∼30% of the first α-proton) into the α-position, as a function of time. The observed pseudo-first-order rate constants correlated to the [basic form] of the buffer and yielded the second-order rate constants for the general base-catalyzed enolization of cyclobutanone for four tertiary amine buffers. A Brønsted β-value of 0.59 was determined from the second-order rate constants determined. Comparison of the results for cyclobutanone to those previously reported for acetone and a 1-phenylacetone derivative, under similar conditions, indicated that the ring strain of the carbocycle appeared to have only a small effect on the general base-catalyzed rate constants for enolization. The similarity of the rate constants for the general base-catalyzed enolization of cyclobutanone to those determined for acetone allowed for an estimation of the limits of the rate constant for protonation of the enolate intermediate of cyclobutanone by the conjugate acid of 3-quinuclidinone (k BH = 5 × 108 − 2 × 109 M−1 s−1). Combining the rate constants for deprotonation of cyclobutanone (k B) and protonation of the enolate of cyclobutanone (k BH) by 3-quinuclidinone and its conjugate acid, the pK a of the α-protons of cyclobutanone has been estimated to be pK a = 19.7−20.2.

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Hydration and Hydrolysis of α-Oxo Carboxylic Acid Derivatives and Conjugate Addition to α,β-Unsaturated Carbonyl Compounds: A Density Functional Study

Janoschek

Fabian

1999

J. Org. Chem.

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Hydration of the keto group as well as hydrolysis (ester and amide) of alpha-oxo carboxylic acid derivatives has been studied by density functional theory (B3LYP/6-31G and B3LYP/6-311G). Both uncatalyzed as well as water-assisted processes have been considered. Solvent effects were approximated by the self-consistent isodensity surface polarized continuum (SCIPCM) model. For hydrolysis reactions a concerted as well as a stepwise mechanism was calculated. In the latter one, addition of the nucleophile to a tetrahedral intermediate was found to be rate determining. In uncatalyzed processes both concerted and stepwise mechanisms are calculated to have comparable activation energies and free enthalpies. In catalyzed reactions the stepwise mechanism is predicted to be considerably more favorable. Hydration of the alpha-oxo group should be much more feasible than either ester or amide hydrolysis.

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Computational investigations of carbonyl reactions: Comparison between nucleophilic addition versus enolate formation in the reaction of acetaldehyde with hydroxide ion

Cited by 7 publications

References 28 publications

Ab initio study of the alkaline hydrolysis of a thio-β-lactam structure

Ab initio study of the alkaline hydrolysis of a thio-β-lactam structure

Determination of the pK_aof Cyclobutanone: Brønsted Correlation of the General Base-Catalyzed Enolization in Aqueous Solution and the Effect of Ring Strain

Hydration and Hydrolysis of α-Oxo Carboxylic Acid Derivatives and Conjugate Addition to α,β-Unsaturated Carbonyl Compounds: A Density Functional Study

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Computational investigations of carbonyl reactions: Comparison between nucleophilic addition versus enolate formation in the reaction of acetaldehyde with hydroxide ion

Cited by 7 publications

References 28 publications

Ab initio study of the alkaline hydrolysis of a thio-β-lactam structure

Ab initio study of the alkaline hydrolysis of a thio-β-lactam structure

Determination of the pKaof Cyclobutanone: Brønsted Correlation of the General Base-Catalyzed Enolization in Aqueous Solution and the Effect of Ring Strain

Hydration and Hydrolysis of α-Oxo Carboxylic Acid Derivatives and Conjugate Addition to α,β-Unsaturated Carbonyl Compounds: A Density Functional Study

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Determination of the pK_aof Cyclobutanone: Brønsted Correlation of the General Base-Catalyzed Enolization in Aqueous Solution and the Effect of Ring Strain