Nucleophilic Substitution of Alkyl Halides (Part 2)

Observations in Substitution Reactions Single enantiomer of a starting material resulted in two situations (generally) Single enantiomer of product (optically active) Racemic products (optically inactive) Rates showed two opposing trends Primary halides reacted rapidly and tertiary halides reacted slowly Primary halides reacted slowly and tertiary halides reacted rapidly Kinetics showed two situations First order dependence on the nucleophile No concentration dependence on the nucleophile

S N 2 Mechanism Bimolecular reaction Rate = k [alkyl halide] 1 [nucleophile] 1 Inversion of chirality at carbon Reactivity of alkyl halides: 1° > 2° > 3°

S N 1 Mechanism Two step mechanism Unimolecular Rate = k [alkyl halide] 1 Racemization of chirality at carbon Reactivity of alkyl halides: 3° > 2° > 1° Step #1: Rate Determining Step Step #2

Transition States SN2SN2SN1SN1

Alkyl Halide (Substrate) Steric effects: carbon is being attacked by the nucleophile in an S N 2 mechanism Steric strain experienced by nucleophile increases in the order: 1° < 2° << 3° So reactivity is CH 3 X > 1° > 2° Carbocation: intermediate in the S N 1 mechanism Electron-donation by attached carbons stabilizes carbocation intermediates: 3° > 2° > 1°

Hammond’s Postulate

Allylic Halides SN2SN2 SN1SN1

Benzylic Halides SN2SN2 SN1SN1

Transition States vs. Solvents SN2SN2SN1SN1 Both mechanisms have polar transition states which are stabilized by solvents that possess dipole moments= Polar Solvents Non-polar solvents: both mechanisms are very slow in these solvents (e.g., hexane, benzene, CCl 4 )

Best Solvents for S N 2

Best Solvents for S N 1

Nucleophile Concentration and reactivity of the nucleophile important in S N 2 Good electon-pair donors but weak bases Anions >> neutral nucleophiles Nucleophile is not involved in the rate determining step of the S N 1 mechanism Poor electron-pair donors often favor S N 1 Conjugate acids of nucleophiles especially as solvents

Leaving Groups I  > Br  >> Cl  >> F  > OH  P-toluenesulfonate (OTs  ) H2OH2O

Alcohols as Substrates