2.3. Keto-Enol Tautomerism
If there are hydrogens at the position adjacent to a carbonyl they are made acidic by the carbonyl; a combination of induction and resonance stabilization of the conjugate base makes protons next to carbonyls more acidic than usual. This acidity leads to a phenomenon common to all carbonyl-containing functional groups.
Recall that molecules that have the same chemical formula BUT their atoms are connected in a different sequence are called constitutional isomers. Tautomers are constitutional isomers that can readily interconvert. One constitutional isomer becomes another through a process called tautomerization. All carbonyl-containing functional groups (that have a hydrogen adjacent to the carbonyl) exist as a pair of constitutional isomers that interconvert by moving a hydrogen from the adjacent carbon to the oxygen of the carbonyl (Scheme 2.1).
Scheme 2.1 – Keto-Enol Tautomerism with Keto and Enol Tautomers of Acetone.
The isomer that contains the carbonyl is called the “keto” form (from ketone). The other isomer is called the “enol” form (from alkene and alcohol). These names apply even when the functional group is not a ketone (Scheme 2.2). Technically, there are specific names used for some pairings depending on the exact functional group. These are not commonly used and are not required at an introductory level. However, they may be encountered in other sources.
Scheme 2.2 – Examples of Keto-Enol Tautomerism with Other Carbonyl-Containing Functional Groups.
The two forms are able to rapidly interconvert because of the acidity caused by the carbonyl.
The interconversion can be catalyzed by base (Scheme 2.3). The base removes a hydrogen from the carbon adjacent to the carbonyl (acid/electrophile). This creates a resonance-stabilized anion. The anion then acts as a base/nucleophile at the oxygen, regaining the hydrogen there instead. This regenerates the base catalyst and creates the enol tautomer. The process is fully reversible.
Scheme 2.3 – General Reaction Mechanism for Base-Catalyzed Keto-Enol Tautomerization of Acetone.
The interconversion can be catalyzed by acid (Scheme 2.4). The process is the same as the base-catalyzed mechanism but with the opposite order of steps. The oxygen of the carbonyl (base/nucleophile) removes a hydrogen from the acid catalyst. This creates a resonance-stabilized cation. The conjugate base of the acid then acts as a base/nucleophile to remove a hydrogen from the carbon adjacent to the carbonyl instead. This regenerates the acid catalyst and creates the enol tautomer. The process is fully reversible.
Scheme 2.4 – General Reaction Mechanism for Acid-Catalyzed Keto-Enol Tautomerization of Acetone.
The keto and enol forms are in equilibrium with one another. However, they are NOT energetically equivalent. Typically the keto form is significantly more stable. As a result, even at equilibrium the amount of compound in the enol tautomer is usually very small.
The enol tautomer of a carbonyl-containing functional group is nucleophilic (Figure 2.6). In principle the enol is nucleophilic at both the oxygen and the carbon of the alkene (the α carbon). In practice, when acting as a nucleophile in chemical reactions the enol will preferentially attack from the carbon rather than the oxygen.
Figure 2.6 – Resonance forms of a Generic Enol Highlighting Nucleophilicity at the Alpha Carbon.
If the hydrogen of the enol is removed the resulting anion is called an enolate (Figure 2.7). Enolates are many times more nucleophilic than enols. They also preferentially act as nucleophiles at the α carbon.
Figure 2.7 – Resonance forms of a Generic Enolate Highlighting Nucleophilicity at the Alpha Carbon.
Depending on the specifics of the reaction, some chemical reactions work with enols but not enolates, some with both enols and enolates, and some with enolates but not enols. Chemical reactions using enols and enolates (see Sections 2.6-2.9) require consideration of which would be better suited for the task.
