Elimination vs. Substitution

Reagent: Nucleophile ONLY

• Cl^-

• Br^-

• I^-

• HS^-

• RS^-

• H2S

• RSH

• Think SUBSTITUTION

Reagent: Base ONLY

• t-BuO^-

• H^-

• Think ELIMINATION

Reagent: Strong Nu AND Strong Base

• Think BIMOLECULAR (S_N2 and E2)

• HO^-

• MeO^-

• EtO^-

• t-BuO^- (sterically hindered, MUCH more likely to be used as a base)

Reagent: Weak Nu AND Weak Base

• H₂O

• MeOH

• EtOH

• Think UNIMOLECULAR (S_N1 and E1)

S_N2

• Nucleophile only → 1° → S_N2 (only option)

• Nucleophile only → 2° → S_N2 (only option)

• Strong Nu/Strong base → 1° → S_N2 (major; unless t-BuOK is used)

• Strong Nu/Strong base → 2° → S_N2 (minor)

S_N1

• Nucleophile only → 3° → S_N1 (only option)

• Weak Nu/Weak Base → 3° → S_N1 (with E1 likely)

E2

• Base only → 1° → E2 (only option)

• Base only → 2° → E2 (only option)

• Base only → 3° → E2 (only option)

• These are GENERALLY strong bases, which is why E2 tends to occur

E1

• Weak Nu/Weak Base: 3° → E1 (with S_N1 likely)

Common Strong Nucelophiles

• I^-

• Br^-

• Cl^-

• HS^-

• H₂S

• RSH

• HO^-

• RO^-

• N≡C^-

Common Weak Nucleophiles

• F^-

• H₂O

• ROH

Good Leaving Groups

Conjugate bases of very strong acids

• I^-

• Br^-

• Cl^-

• H₂O

• Sulfate ions (tosylate, mesylate, triflate)

Bad Leaving Groups

Conjugate bases of weak acids

• HO^-

• EtO^-

• t-BuO^-

• N_H2^-

Polar Aprotic Solvents

Helps S_N2 reactions occur significantly faster; there’s NO proton attached to electronegative atom

• Acetone

• DMSO

• DME

• DMF

Polar Protic Solvents

Protons attached to the electronegative atom

• EtOH

• MeOH

• Carboxylic acid