Hofmann Elimination
- “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
- Cis and Trans
- Conformations
- Conjugate Addition
- Curved Arrow Refresher
- Curved Arrows
- Decarboxylation
- 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
- 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
- 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
- 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
- Stereochemistry
- 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
Two key reactions of amines to talk about today. They’re very different reactions, but often seen together.
First of all, yesterday I said that amines are good nucleophiles. Waaaay back in Org 1 you probably talked about nucleophilic substitution (remember the SN2? backside attack?)
Amines, being nucleophiles, can certainly participate in this reaction with alkyl halides. However, you probably didn’t see many examples of amines in this reaction. Why not?
Well, amines have the same relationship with alkyl halides that I have with potato chips. It’s hard to have just one.
A primary amine (like that shown) will react with an alkyl halide like CH3-I, to make a secondary amine. Once that’s formed, however, the secondary amine is still a nucleophile. It can react with another alkyl halide, making a tertiary amine. Which can then add a final alkyl halide until we have made a nitrogen with four alkyl groups, and there aren’t any lone pairs left. I didn’t draw out the full mechanism – it’s here.
It’s impossible to get this reaction to just stop after one alkylation. So even if you add only one equivalent, you’ll still get a mixture of product. If we add a large excess of alkyl halide, we can get one product – the “quaternary ammonium” salt.
Quaternary ammonium salts are not very exciting chemical species. However, they do perform one interesting reaction.
The ammonium (NR3)+ is a good leaving group. Treatment with a base will lead to E2 reactions, where we form an alkene. This is called the Hofmann elimination. A common base for this is silver oxide (Ag2O) although many other bases will also work.
This E2, however, has a twist. Unlike most E2 reactions, which form the most substituted double bond (the Zaitsev product) these ones end up always forming the least substituted double bond. That’s weird, because the Zaitsev is usually favored due to more substituted alkenes being more stable. So what’s going on here?
The answer lies in the transition states. If you compare the transition states leading to the two alkenes (and draw out our old friend, the Newman Projection) you’ll find that the transition state leading to the Zaitsev product has more steric hindrance. That’s because the leaving group is very bulky, and it has a steric clash with the carbons adjacent to it in the Zaitsev product. Meanwhile, the Hofmann elimination transition state doesn’t have this problem with steric hindrance. So the transition state is lower in energy, and therefore, the product is formed at a greater rate.
Bottom line: ammonium salts are bulky leaving groups, and from them we obtain the “non-Zaitsev” alkene.
Tomorrow: a nifty way around this problem helps us make primary amines.
Thanks for reading! James