Ch. 22 - Condensation ChemistrySee 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

Robinson annulation is a reaction between an enolate and an alpha, beta-unsaturated ketone that forms a ring. 

Robinson annulation mechanism 

The very first part of Robinson annulation is basically a base-catalyzed Michael reaction, in which an enolate attacks a conjugated ketone or aldehyde. Let's check it out! To be clear, we're not looking at the actual Robinson annulation just yet. 

Michael AdditionMichael Addition

Okay, let's get to the heart of this post: Robinson annulation. Let’s take a look at the mechanism. The very first step is the addition of base to remove the alpha proton to form the enolate. Once the enolate is formed, it can can attack the electrophilic enone. We’ll use an alkoxide as our base in this example. 

Enolate-formation-and-conjugate-additionEnolate Formation and Conjugate Addition

Second enone formationSecond Enone Formation

From there, another enone is formed. That enol is actually deprotonated, but there’s something to keep in mind: the enolate that forms is the one that actually forms the ring, so we need to count the number of atoms from the enolate to the carbonyl. The most stable ring-size is 6, so we want to get as close to that as possible.  

enolate-formation-and-nucleophilic-additionEnolate Formation and Nucleophilic Addition

The green alpha-hydrogen is deprotonated, and it then attacks the carbonyl leaving us with an alcohol. 

Ring Formation and DehydrationRing Formation and Dehydration

That alcohol undergoes dehydration through an E1cB mechanism, which is a special kind of elimination, and we end up with yet another enone! Notice that the alcohol dehydrated “toward” the ketone. Why? Resonance! Conjugated molecules are more stable, so the enone is favored over the isolated double bond. 

Here's the whole mechanism in one piece to see it in all its glory: 

Full mechanismFull mechanism

Heads up: applications for the Robinson annulation include building molecules like steroids—you know, since they’ve got so many rings. 

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
A scientist needed to prepare large quantities of chemical intermediate I through the process shown below. What is the structure of intermediate  I?
In the following Robinson Annulation, compound A could be formed but is not a final product of the reaction. Why? a) A is formed irreversibly, but only in small amounts contributing to a lower yield of the reaction. b) A is too strained and is never formed. c) A is formed reversibly, but cannot undergo elimination, so it reverts back the prior intermediate. d) A can only be formed from the less favorable enolate and is therefore only a minor product of the reaction. e) The bonds in A are way too long and a molecule would never want to look that silly, so it doesn’t form.
Draw the intramolecular condensation product formed when 2,6-heptanedione is heated with aqueous sodium hydroxide.
Draw the product for the following Robinson reaction.
Predict the product of the following reaction
 Provide a mechanism for the following transformation. Show all important flows of electrons, charges and intermediates. Where indicated, (in the structure-n-a- box)- draw the intermediates.
For the following reaction, two products are formed, in addition to water. If the oxygen of the enone is labeled with an isotope (18O for example), where will the label appear in the product? a) B and E only b) B and D only c) A and C only d) A, B, C, and D e) all 5 positions
Illlustrate the Robinson Annulation. Show two typical reactants and the resulting product and indicate where the atoms from the starting material end up in the product. A full mechanism is not necessary.
Complete the mechanism for the following Robinson Annulation Reaction. Draw all the arrows to indicate movement of all electrons, write all lone pairs, all formal charges, and all products for each step. If a new chiral center is created in an intermediate or in the product indicate with an * (ASTERIK).
Provide a mechanism for the following transformation. Show all important flows of electrons, charges and intermediates. Where indicated, (in the structure-n-a-box) draw the intermediates.
For each of the following reactions, provide the missing starting material, reagent, or major product in the box provided.
Which two components can be used to prepare the following compound through a Robinson annulation reaction?