Ketones on Acid
- “Initial Tails” and “Final Heads”
- 3 Ways To Make OH A Better Leaving Group
- A Simple Formula For 7 Important Aldehyde/Ketone Reactions
- 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
- 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
- Cis and Trans
- Conjugate Addition
- Curved Arrow Refresher
- Curved Arrows
- Determining Aromaticity
- Diels Alder Reaction – 1
- Dipoles: Polar vs. Covalent Bonding
- E2 Reactions
- Electronegativity Is Greed For Electrons
- Electrophilic Aromatic Substitution – Directing Groups
- Elimination Reactions
- Enantiocats and Diastereocats
- Epoxides – Basic and Acidic
- Evaluating Resonance Forms
- Figuring Out The Fischer
- Find That Which Is Hidden
- Formal Charge
- Frost Circles
- Gabriel Synthesis
- 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 Shortcut
- 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
- Pi Donation
- 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
- 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
- Strong Acid Strong Base
- Strong And Weak Oxidants
- Strong and Weak Reductants
- Stronger Donor Wins
- 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
- 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
Acids are like an aphrodisiac for carbonyl compounds: it makes them more likely to react with nucleophiles.
Let me explain.
I said the last two days that carbonyl carbons are important electrophiles: they bear a partial positive charge.
Now, I’m going to show how you can make them even more electrophilic – more reactive. This means that reactions that normally wouldn’t happen, will now happen.
First, a question: How do we make electrophiles more electrophilic?
Simple: we take electrons away from them!
How can we take electrons away? With carbonyls, the answer might be a bit counterintuitive. We’re going to add acid to the oxygen, and this will make the carbon more electron-poor.
Sounds weird, but it actually makes sense when you think about it.
Think about the resonance forms of the carbonyl:
- its most stable resonance form has a carbon-oxygen double bond (neutral) and the less stable resonance form has a positive charge on carbon and a negative charge on oxygen.
- So the “resonance hybrid” has a small partial positive charge on carbon, because of that resonance form on the right.
Now let’s add acid – say, H+ .
- The oxygen will go from “owning” a pair of electrons, to “sharing” it with the hydrogen.
- So it formally “loses” an electron to give a positively charged oxygen. (Watch out though: remember that “formal charge” doesn’t tell us about electron densities: electronegativity does. So even though there’s a “formal charge” of +1 on the oxygen, it’s still electron-rich compared to hydrogen and carbon)
With me so far? If this isn’t clear, write me! If everything is OK, let’s keep going.
Think about what this does to the resonance forms.
- Now, both resonance forms have a charge of +1 . This means that the right-hand resonance form (with a positive charge on carbon), although still less stable than the resonance form on the left (where everything has a full octet) will be more significant than before.
- And this means it will make a greater contribution to the resonance hybrid, which means that the carbon will have a greater partial positive charge.
That means that the carbon will be more electrophilic – and therefore, react faster with nucleophiles!
So why is this important? It’s important because it allows certain reactions to happen that would never proceed otherwise.
When will it be important? Really soon! It’s important for the formation of acetals, which is coming right up. It will also be KEY for the next few chapters involving carbonyl chemistry.
Tomorrow: let’s talk about the SECOND-most important mechanism step for carbonyls.
Thanks for reading! James