Keto-enol equilibria acid-catalyzed

Regarding the first problem, the most elemental treatment consists of focusing on a few points on the gas-phase potential energy hypersurface, namely, the reactants, transition state structures and products. As an example, we will mention the work [35,36] that was done on the Meyer-Schuster reaction, an acid catalyzed rearrangement of a-acetylenic secondary and tertiary alcohols to a.p-unsaturatcd carbonyl compounds, in which the solvent plays an active role. This reaction comprises four steps. In the first, a rapid protonation takes place at the hydroxyl group. The second, which is the rate limiting step, is an apparent 1, 3-shift of the protonated hydroxyl group from carbon Ci to carbon C3. The third step is presumably a rapid allenol deprotonation, followed by a keto-enol equilibrium that leads to the final product. 

In Summary Aldehydes and ketones are in equilibrium with their enol forms, which are roughly 10 kcal mol less stable. Keto-enol equilibration is catalyzed by acid or base. Enolization allows for easy H-D exchange in D2O and canses isomerization at stereocenters next to the carbonyl group. 

The initial product has a hydroxy group attached to a carbon-carbon double bond. Compounds such as this are called enols (ene + ol) and are very labile—they cannot usually be isolated. Enols such as this spontaneously rearrange to the more stable ketone isomer. The ketone and the enol are termed tautomers. This reaction, which simply involves the movement of a proton and a double bond, is called a keto—enol tautomerization and is usually very fast. In most cases the ketone is much more stable, and the amount of enol present at equilibrium is not detectable by most methods. The mechanism for this tautomerization in acid is shown in Figure 11.6. The mercury-catalyzed hydration of alkynes is a good method for the preparation of ketones, as shown in the following example ... 

Tautomerization is the shift of an H from a carbon adjacent to a carbon-heteroatom double bond to the heteroatom itself (and the reverse). It is an acid- or base-catalyzed equilibrium. Two examples are the keto/enol pair (Z = oxygen) and the imine/enamine pair (Z = nitrogen). Base catalysis goes via the enolate anion. 

When an alkyne undergoes the acid-catalyzed addition of water, the product of the reaction is an enol. The enol immediately rearranges to a ketone. A ketone is a compound that has two alkyl groups bonded to a carbonyl (C=0) group. An aldehyde is a compound that has at least one hydrogen bonded to a carbonyl group. The ketone and enol are called keto-enol tautomers they differ in the location of a double bond and a hydrogen. Interconversion of the tautomers is called tautomerization. The keto tautomer predominates at equilibrium. Terminal alkynes add water if mercuric ion is added to the acidic mixture. In hydroboration-oxidation, H is not the electrophile, H is the nucleophile. Consequently, mercuric-ion-catalyzed addition of water to a terminal alkyne produces a ketone, whereas hydroboration-oxidation of a terminal alkyne produces an aldehyde. 

Both an acidic and an alkaline environment will catalyze a shift of tiie equilibrium to the right, making the portion of the molecule actually present in the enol form higher. This equilibrium runs through a number of steps that are different depending on whether the solution is acid or alkaline. If the solution is alkaline, the keto-enol interconversion occurs via the enolate ion. In this enolate ion a proton is abstracted from either the alcohol group or the a-carbon of the enol form, and the two forms are stabilized by resonance (Figure 3.17.3). 

Collapse of the CTI forms the neutral P-keto ester product that will eventually be isolated, but the reaction mechanism does not stop here. Since the 1,3-dicarbonyl product has a highly acidic alpha proton (a to two EWGs), it becomes deprotonated in the basic reaction conditions to give a stabilized enolate. This deprotonation step is a necessary one, as it drives the equilibrium in the forward direction the Claisen condensation will not occur if there are not at least two alpha protons present in the ester starting material, and the acid-catalyzed Claisen condensation does not exist. Upon treatment with a mild aqueous workup, the enolate is protonated and the neutral P-keto ester product can be isolated. 

Keto-enol tautomerization is an equilibrium process that is catalyzed by even trace amounts of acid (or base). Glassware that is scrupulously cleaned will still have trace amounts of acid or base adsorbed to its surface. As a result, it is extremely difficult to prevent a keto-enol tautomerization from reaching equilibrium. 

Ketones and aldehydes bearing a hydrogens are in equilibrium with their enol forms, although for simple ketones and aldehydes the carbonyl forms are greatly favored. This equilibrium is the keto—enol tautomerization. Equilibration with the enol form can be either acid- or base-catalyzed. The enol form can be favored in special cases. Esters and other acid derivatives also have acidic a hydrogens. LDA is a strong base that can be used to drive ketones, aldehydes, or esters completely to their corresponding enolates. 

The aldol condensation and related reactions are among the most important, and ubiquitous, construction reactions in organic synthesis. In these condensations, the carbonyl compound acts as both nucleophile and electrophile—the enol or enolate is the nucleophile, and the keto form is the electrophile. The reaction works with enolizable aldehydes (Figure 17.24) or ketones (Figure 17.25) and may be catalyzed by either acid or base. Almost all of the steps we write are equilibria—how can we persuade the reaction to go to completion In the base-catalyzed reaction, a catalyst such as barium hydroxide is placed inside a Soxhlet thimble, as in Figure 17.26. The reaction mixture is heated so that the acetone refluxes, but the product does not. Thus only the SM, and not the product, comes into contact with the catalyst, ensuring that the reverse reaction does not occur. Note that in the acid-catalyzed processes, it is common for the product to be dehydrated under the reaction conditions—this usually pulls the equilibrium over to the product. The mechanism of the elimination reaction may be El or E2 depending on the... 

Equilibrium favors the keto form largely because a C=0 is much stronger than a C=C. Tautomerization, the process of converting one tautomer into another, is catalyzed by both acid and base. Under the strongly acidic conditions of hydration, tautomerization of the enol to the keto form occurs rapidly by a two-step process protonation, followed by deprotonation as shown in Mechanism 11.3. 

Enolization can be either acid- or base-catalyzed, and general catalysis mechanisms have been observed. With general-base catalysis, deprotonation of the a-carbon in the first step is rate-determining. Protonation of the enolate oxygen gives the enol (Eq. 11.1). Both reactions in the second equilibrium of Eq. 11.1 are faster than the initial deprotonation of the a-carbon of the keto form. 

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