Ch. 21 - Enolate Chemistry: Reactions at the Alpha-Carbon See all chapters
All Chapters
Ch. 1 - A Review of General Chemistry
Ch. 2 - Molecular Representations
Ch. 3 - Acids and Bases
Ch. 4 - Alkanes and Cycloalkanes
Ch. 5 - Chirality
Ch. 6 - Thermodynamics and Kinetics
Ch. 7 - Substitution Reactions
Ch. 8 - Elimination Reactions
Ch. 9 - Alkenes and Alkynes
Ch. 10 - Addition Reactions
Ch. 11 - Radical Reactions
Ch. 12 - Alcohols, Ethers, Epoxides and Thiols
Ch. 13 - Alcohols and Carbonyl Compounds
Ch. 14 - Synthetic Techniques
Ch. 15 - Analytical Techniques: IR, NMR, Mass Spect
Ch. 16 - Conjugated Systems
Ch. 17 - Aromaticity
Ch. 18 - Reactions of Aromatics: EAS and Beyond
Ch. 19 - Aldehydes and Ketones: Nucleophilic Addition
Ch. 20 - Carboxylic Acid Derivatives: NAS
Ch. 21 - Enolate Chemistry: Reactions at the Alpha-Carbon
Ch. 22 - Condensation Chemistry
Ch. 23 - Amines
Ch. 24 - Carbohydrates
Ch. 25 - Phenols
Ch. 26 - Amino Acids, Peptides, and Proteins
Johnny Betancourt

Tautomerization is the name given to the process by which keto and enol forms interconvert. The keto and enol forms are constitutional isomers that reach an equilibrium in acidic or basic conditions. 

Keto-Enol tautomerization 

Tautomerization is possible in both acidic and basic solution. Let’s look at the mechanisms to go from ketone to enol and back to ketone. The keto form is the familiar carbonyl, while the enol form is basically a vinyl alcohol. 

Acid-catalyzed mechanismAcid-catalyzed mechanism

The first step in the acidic mechanism is protonation. Heads up: H3O+ is the same thing as H2O and H+. Once the protonated carbonyl is formed, the conjugate base will remove the acidic alpha hydrogen. This forms a bond between the carbonyl carbon and the alpha carbon, and the carbonyl’s pi-electrons are kicked onto the oxygen to form the enol. 

To go back to the keto form the oxygen reforms the carbonyl, and the C=C bond’s pi-electrons deprotonate the H3O+ to form H2O again. Then the water removes the proton from the oxygen and voila! You’ve got nice C-C and C=O bonds again. 

Base-catalyzed mechanismBase-catalyzed mechanism

The base-catalyzed mechanism starts with the deprotonation of the alpha carbon by a base like –OH. This deprotonated enol is called an enolate, and it’s found extensively in condensation reactions. The anionic oxygen grabs the hydrogen from the conjugate acid, and now we’ve got ourselves an enol. 

To go back to the keto form, the alcohol is deprotonated. Then the anionic oxygen kicks a lone pair down to reform the carbonyl, and the C=C bond’s pi-electrons are used to deprotonate the H2O to form –OH again. 

Equilibrium direction

​​Keto-enol equilibrium​​Keto-enol equilibrium

In general, the keto form predominates in equilibrium because it is lower in energy. You can even think about this in terms of an acid-base reaction. Equilibrium direction goes from more acidic to less acidic, so it makes sense that the equilibrium would favor the keto form. An alpha hydrogen’s pka is about 20, and an alcohol’s pka is about 16. The alcohol is about ten thousand times as acidic as the alpha carbon. 

Beta-dicarbonyl tautomerizationBeta-dicarbonyl tautomerization

The equilibrium of beta dicarbonyls will actually shift toward the enol form. Why? The enol form is conjugated from one oxygen to the other though the c-c pi-bond, and it also has that hydrogen attached to one of the oxygens which results in hydrogen bonding to the other oxygen. 

Imine-Enamine tautomerization

Imine-enamine tautomerizationImine-enamine tautomerization

Imines and enamines can actually tautomerize just like ketones and enols. Imine-enamine tautomerization actually plays a pretty big role in enamine alkylation through the Stork enamine mechanism. 

P.S. Sometimes tautomerization can occur in DNA base pairs. Normally guanine pairs with cytosine, but the enol form of guanine will actually pair with thymine. Just another way Genetics can get pretty complicated. 

Johnny Betancourt

Johnny got his start tutoring Organic in 2006 when he was a Teaching Assistant. He graduated in Chemistry from FIU and finished up his UF Doctor of Pharmacy last year. He now enjoys helping thousands of students crush mechanisms, while moonlighting as a clinical pharmacist on weekends.

Additional Problems
How many α-hydrogens does 2-hexanone have? a 1 b 2 c 3 d 4 e 5  
Which of the following is not correct? a Tautomerization is catalyzed by both acids and bases. b Tautomers are constitutional isomers. c Tautomers rapidly interconvert. d The enol form is generally more stable. e All of the above are correct with respect to tautomers.
Draw the enol tautomer for the following ketone:
Write out the mechanism for the following transformation.
Write out the mechanism for the following transformation.
How many acidic protons (pKa ≤ 20) are in the following compound?
Consider each of the equilibria shown below. Does the equilibrium lie to the left or to the right?
How many tautomers can you draw? 
Identify the keto form of the following enol. a 1-penten-3-one b (E)-3-penten-2-one c 2-pentanone d (E)-3-pentenal e (Z)-3-penten-2-one
Consider the structural formula of acetaldehyde below. (a) Give a chemical equation for the reaction between hydroxide ion (HO -) and acetaldehyde in which HO- acts as a Lewis base and acetaldehyde acts as a Lewis acid. IMPORTANT: The Lewis base that you give cannot be a Bronsted-Lowry base; the Lewis acid that you give cannot be a Bronsted-Lowry acid. Note: Use Lewis structures for each reactant/product and use curved arrows appropriately.            (b) Using Lewis structures for each reactant and each product and using curved arrows appropriately to show the flow of electrons in the reactants, give a chemical equation for the reaction between hydroxide ion (HO -) and acetaldehyde in which HO- acts as a Bronsted-Lowry base and acetaldehyde acts as a Bronsted-Lowry acid. Do not give the same answer that you gave in the first part of this question.           
Estimate Keq for the following reaction and explain if the equilibrium favors the reactants or the products. pKa α-H cyclohexanone 20; pKa HCN 9; pKa β-H cyclohexanone 40 
The following reaction process is an example of A. Resonance B. Conjugation C. Oxidation D. Acetalization E. Tautomerism
Which represents a keto-enol tautomerization?
Refer to the reaction drawn below to answer the following questions.   In the presence of acid or a base a ketone can be converted into an ___________. This process is called _______________________. The ketone predominates because _______________________________________________________.  
Which of the following is (are) a keto-enol tautomeric pair(s)?
Which of the following is a keto-enol tautomeric pair?
The final step in the hydration of an alkyne under both acidic and basic conditions is the tautomerization of an enol intermediate to give the corresponding carbonyl. Provide an arrow-pushing mechanism for the tautomerization under acidic conditions. 
Provide a mechanism for the following reaction. Be sure to include all intermediates, formal charges and arrows depicting electron movement.
Draw the enol tautomers of the following ketone
Addition of water to an alkyne gives a keto-enol tautomer product. Draw the ketone that is in equilibrium with the given enol.  
Draw the enol that is in equilibrium with the given aldehyde.
Draw the structural formula of the enol tautomer of cyclopentanone. 
Carbonyl Compounds: Draw the keto tautomer of cyclohexenol. 
Draw the keto tautomeric form of the following compound: 
Carbonyl Compounds: Draw the ketotautomer of (2z)-but-2-en-2ol
Draw the keto and enol forms of propanone.