sn1/sn2/e1/e2 – Nucleophile

• “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
  • Conjugation
• 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

OK, now that we’ve asked the first question about SN1/SN2/E1/E2, we need to ask the second question.

Here it is: Is the nucleophile strong or weak?

Remember that the rate-limiting step in the SN2 and E2 reactions involves both the nucleophile (base) and the alkyl halide, whereas the E1 and SN1 just require the alkyl halide (the leaving group leaves!)

So the E2 and SN2 reactions require “stronger” nucleophiles/bases than the SN1 and E1 reactions. 

So what makes the difference between a strong nucleophile and a weak one?

Strong nucleophiles generally bear a negative charge, such as RO(-),  (-)CN, and (-)SR. By the way, you might not see the negative charge – it’s often got a counterion (a spectator ion) such as Na, Li, or K. So if you see NaCN, KOCH3, and so on, these count as strong nucleophiles too.

Weak nucleophiles are neutral and don’t bear a charge. Some examples are CH3OH, H2O, and CH3SH. In this category I’d also put acids such as H2SO4 and HCl.

So let’s look at the 4 examples I started with yesterday.

Example 1 uses NaCN (a strong nucleophile). We’ve already ruled out the SN1 and E1 here because it’s primary. As it turns out, NC(-) is quite a weak base, so the E2 won’t happen here either, but we’ll deal with that in the summary at the end of the week.

Example 2 uses KOEt (strong nucleophile). So we can rule out the SN1 and E1 here as well.

Example 3 uses H2SO4. So we can rule out the E2, in addition to the SN2 we ruled out earlier because it’s tertiary.

Example 4 uses CH3OH. So we can rule out the SN2 and E2.

Already, for each of these 4 examples, we’ve got it down from 4 possibilities to 2. Tomorrow, we’ll look at the solvent, and winnow it down even more.

Thanks for reading! James