Substitution Reactions

SN2

• Concerted reaction (all bond breaking/forming happens in the one step)

• Requires a strong nucleophile (R-O^-)

• Me > Primary > Secondary (Tertiary substrate = highly unlikely)

• Rate dependent on both Nu and substrate (rate = k_r[substrate][Nu])

• Stereochemistry inverts (Nu attacks from the back, flipping the configuration; think of an umbrella flipping up in the wind)

SN1

• Weak nucleophile (R-OH, H2O) are ok

• Tertiary > Secondary substrates (Me and primary substrates not allowed)

• Rate dependent only on substrate (rate = k_r[substrate])

• RDS = when the leaving group leaves

• Products are racemic

Nucleophile Strength

Conjugate bases are stronger that conjugate acids

• An alkoxide (R - CH2 - O^-) is stronger than an alcohol (R - CH2 - OH)

Weak Nucleophiles

• H2O

• ROH

• F^-

Intermediate Nucleophiles

• RCO2H

• Cl^-

• RCO2^-

• RSH

• RNH2

• Br^-

Strong Nucleophiles

• RO^-

• HO^-

• R3N

• C^-≡N

• R—≡^-

• I^-

• RS^-

• HS^-

• NH2^-

• PR3

Guiding Trends of Nucleophile Strength

• High electron density (a - charge) = a good Nu

• Across the periodic table, Nu strength decreases

• Down the periodic table, Nu strength increases

• More substitution on N, Nu strength increases

Substitution

Less substituents = a better nucleophile

• R—O^- is a better Nu than tertbutyl—R—O^-

Electrophile Strength

• 1^o > 2^o > 3^o

• A primary substrate is a better electrophile because it’s easier for the nucleophile to attack (there’s less in the way)

Good Leaving Groups

Things that are very weak bases 

• Cl^-, Br^-, I^-

• Sulfates

• Phosphates

• HSO4^-

Bad Leaving Groups

Things that are strong bases

• —OH

• —OR

• —NH2