Ranking Nucleophiles and Leaving Groups, Hammond's Postulate

What Makes a Good Nucleophile?+ +1. Wants to give away electrons (good Lewis base).HO -betterthanH 2 O(bases always better thantheir conjugate acids)NH 3betterthanH 2 OHS -betterthanCl -(less electronegative atommeans more willing to give up e - )What Makes a Good Nucleophile?2. More polarizable. (Bigger.)C-X *So, I - is a better nucleophile than F - .

What Makes a Good Nucleophile?3. Not too sterically hindered.t-butoxide anionstrong base,hindered nucleophilemethoxide anionsmaller, attacksmore easilyWhat Makes a Good Nucleophile?4. Not obscured by too polar a solvent.solvent hindersnucleophile fromapproachingelectrophile.So, S N 2 reactions are usually run in medium polarity solvents;polar enough to dissolve ionic species, not so polar to cage the nucleophile.

Some Common NucleophilesComparing Nucleophile Quality withPotential Energy DiagramsbetterWe said HS - thanCl - (based on electronegativity).+++E+reaction coordinate

Comparing Nucleophile Quality withPotential Energy DiagramsLower electronegativitydestabilizes HS - .Some of this isresolved intransition state(but not all).E a (HS - )++EE a (Cl - )So, rate of attack by SH - isgreater than that of Cl - .reaction coordinate++The Hammond PostulateFor similar reactions, differences in starting material orproduct stabilities will be reflected in transition state(to a lesser degree).+Difference instability here……is reflectedhere.++E+Wade 4-14reaction coordinate

What Makes a Good Leaving Group?1. Wants to take electrons (electronegative).Again, lower electronegativitydestabilizes both HS - and S in transition state.E a (RSH)+E a (RCl)+EE a (RSH) > E a (RCl).So, Cl - leaves fasterthan SH - .because of TS stabilization,not product stabilizationreaction coordinate++What Makes a Good Leaving Group?2. Polarizable. (Stabilizes transition state.)good overlap,stabilizationpoor overlapIFSo, I is a better leaving group than F .Interesting consequence: I is both a good nucleophileand a good leaving group.

What Makes a Good Leaving Group?3. Products are stable; S N 2 wouldn’t work much better inreverse.Example:+ +OH is a much better nucleophile than Br ;this reaction would revert if it ever happened.So it doesn’t happen.Steric Hindrance at the S N 2 Reaction CenterInhibits Reaction

Inhibition of S N 2 by Neopentyl Groupsneopentyl bromide(primary, but stillhindered)