The Claisen Condensation
- “Initial Tails” and “Final Heads”
- 3 Ways To Make OH A Better Leaving Group
- A Simple Formula For 7 Important Aldehyde/Ketone Reactions
- Acetoacetic
- Acids (Again!)
- Activating and Deactivating
- Actors In Every Acid Base Reaction
- Addition – Elimination
- Addition Pattern 1 – Carbocations
- Addition pattern 2 – 3 membered rings
- Addition Reactions
- Aldehydes And Ketones – Addition
- Alkene Pattern #3 – The “Concerted” Pathway
- Alkyl Rearrangements
- Alkynes – 3 Patterns
- Alkynes: Deprotonation and SN2
- Amines
- Aromaticity: Lone Pairs
- Avoid These Resonance Mistakes
- Best Way To Form Amines
- Bulky Bases
- Carbocation Stability
- Carbocation Stability Revisited
- Carboxylic Acids are Acids
- Chair Flips
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- Conformations
- Conjugate Addition
- Curved Arrow Refresher
- Curved Arrows
- Decarboxylation
- Determining Aromaticity
- Diels Alder Reaction – 1
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- E2 Reactions
- Electronegativity Is Greed For Electrons
- Electrophilic Aromatic Substitution – Directing Groups
- Elimination Reactions
- Enantiocats and Diastereocats
- Enolates
- Epoxides – Basic and Acidic
- Evaluating Resonance Forms
- Figuring Out The Fischer
- Find That Which Is Hidden
- Formal Charge
- Frost Circles
- Gabriel Synthesis
- Grignards
- Hofmann Elimination
- How Acidity and Basicity Are Related
- How Are These Molecules Related?
- How Stereochemistry matters
- How To Stabilize Negative Charge
- How To Tell Enantiomers From Diastereomers
- Hybridization
- Hybridization Shortcut
- Hydroboration
- Imines and Enamines
- Importance of Stereochemistry
- Intermolecular Forces
- Intro to Resonance
- Ketones on Acid
- Kinetic Thermodynamic
- Making Alcohols Into Good Leaving Groups
- Markovnikov’s rule
- Mechanisms Like Chords
- Mish Mashamine
- More On The E2
- Newman Projections
- Nucleophiles & Electrophiles
- Nucleophilic Aromatic Substitution
- Nucleophilic Aromatic Substitution 2
- Order of Operations!
- Oxidation And Reduction
- Oxidative Cleavage
- Paped
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- Pointers on Free Radical Reactions
- Protecting Groups
- Protecting Groups
- Proton Transfer
- Putting it together (1)
- Putting it together (2)
- Putting it together (3)
- Putting the Newman into ACTION
- Reaction Maps
- Rearrangements
- Recognizing Endo and Exo
- Redraw / Modify
- Robinson Annulation
- Robinson Annulation Mech
- Sigma and Pi Bonding
- SN1 vs SN2
- sn1/sn2 – Putting It Together
- sn1/sn2/e1/e2 – Exceptions
- sn1/sn2/e1/e2 – Nucleophile
- sn1/sn2/e1/e2 – Solvent
- sn1/sn2/e1/e2 – Substrate
- sn1/sn2/e1/e2 – Temperature
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- Strong Acid Strong Base
- Strong And Weak Oxidants
- Strong and Weak Reductants
- Stronger Donor Wins
- Substitution
- Sugars (2)
- Synthesis (1) – “What’s Different?”
- Synthesis (2) – What Reactions?
- Synthesis (3) – Figuring Out The Order
- Synthesis Part 1
- Synthesis Study Buddy
- Synthesis: Walkthrough of A Sample Problem
- Synthesis: Working Backwards
- t-butyl
- Tautomerism
- The 4 Actors In Every Acid-Base Reaction
- The Claisen Condensation
- The E1 Reaction
- The Inflection Point
- The Meso Trap
- The Michael Reaction
- The Nucleophile Adds Twice (to the ester)
- The One-Sentence Summary Of Chemistry
- The Second Most Important Carbonyl Mechanism
- The Single Swap Rule
- The SN1 Reaction
- The SN2 Reaction
- The Wittig Reaction
- Three Exam Tips
- Tips On Building Molecular Orbitals
- Top 10 Skills
- Try The Acid-Base Reaction First
- Two Key Reactions of Enolates
- What makes a good leaving group?
- What Makes A Good Nucleophile?
- What to expect in Org 2
- Work Backwards
- Zaitsev’s Rule
I’ve talked about how important enolates are as nucleophiles, and how they’re used in the Aldol reaction (among others).
Let’s talk about a cousin of the Aldol reaction today. Whereas the Aldol reaction is the addition of enolates to aldehydes or ketones, this reaction is the addition of enolates to esters.
It’s called the Claisen condensation.
It follows the same 2 first steps that the Aldol reaction does.
First, we use a strong base – in this case, EtO(-) , to form the enolate. Next, the enolate adds to another equivalent of the ester (addition reaction).
Now comes the third step, which doesn’t happen in the aldol. Since we’ve got an O(-) and an OR group on the same atom, we can have an elimination reaction occur. This expels RO(-), giving us a ketone. So the RO(-) is regenerated, which can then go and repeat step 1 on another equivalent of ester.
So 3 steps are required: 1) deprotonation 2) addition 3) elimination
It’s one of the most important reactions of esters you’ll encounter. But you can see that it’s built out of the same mechanistic steps we’ve been talking about for the past few weeks. Addition. Elimination. Deprotonation.
thanks for reading! James
P.S.. Common question. Notice that the base here (NaOEt) is the same as the OR on the ester? (OEt). Why is that? Well, if we used a different base such as NaOMe, we’d see “transesterifiation” – that is, replacement of OEt by OCH3. Here, with NaOEt, if transesterification occurs, it’s “invisible”.
P.P.S. The version of the Claisen where we form a ring is called the “Dieckmann condensation”. Same reaction in all respects. Confusing, I know.
P.P.P.S. Reaction Guide – the Claisen condensation