CHEM 2070 Alkyl Halides: Nucleophilic Substitution and Elimination

Substitution reactions

Requires the loss of a leaving group and a nucleophilic attack

Concerted

Happens in one step

Stepwise

Happens in steps

S_N2 Mechanism

Substitution Nucleophilic Bimolecular

The nucleophile always attacks opposite the leading group, “backside attack”

Results in the inversion of a chiral center

Concerted reaction

Rate = k[Nu][substrate]

Increasing the concentration or strength of either increases the rate

Backside attack

Electron density repels the attacking nucleophile from the front-side

The nucleophile must approach the backside to allow electrons to flow from the HOMO of the nucleophile to the LUMO of the electrophile

Proper orbital overlap cannot occur with front-side attack because there is a node on the front-side of the LUMO

S_N1 Reaction

Substitution Nucleophile Unimolecular

Products are a mix of R/S

Rate = k[substrate]

Carbocation formation is rate-determining step

Strength and concentration of Nu don’t matter

What are the features of substitution reactions

1. Carbon attached to the leaving group must be sp³-hybridized

2. Nucleophile

3. Substrate

4. Leaving group

   1. Reaction solvent: most reactions are performed in a solvent

Carbon attached to leaving group MUST be what hybridized?

sp³ !!

Nucleophile

S_N2: requires strong nucleophiles

S_N1: strength does not matter

Strong Nucleophile

X^-, OH^-, SR^-, NR₂^-, ^-C=-N, ^-C=-C-R, RSH

Neutral Nucleophile

H₂O, ROH, RSH, RNH₂

Substrate

Leaving Group

The better the leaving group, the more stable the leading group, the faster the reaction

Reaction solvent: most reactions are performed in a solvent