Unimolecular Nucleophilic Substitution S N 1

Tertiary alkyl halides are very unreactive in substitutions that proceed by the S N 2 mechanism. Do they undergo nucleophilic substitution at all? Yes. But by a mechanism different from S N 2. The most common examples are seen in solvolysis reactions. A question...

The Sn1 Reaction

+ + H Br.... : O : : HH C CH 3 Br C OH : Example of a solvolysis. Hydrolysis of tert-butyl bromide.

rate = k [alkyl halide] First-order kinetics implies a unimolecular rate-determining step. Mechanism is called S N 1, which stands for substitution nucleophilic unimolecular (1) Kinetics and Mechanism

+ Br –.. : :.. unimolecular slow C CH 3 Br.... : C H3CH3CH3CH3C + Mechanism

bimolecular fast C H3CH3CH3CH3C CH 3 + O : : HH C + O : H H Mechanism

proton transfer ROH 2 + carbocation formation R+R+R+R+ ROH carbocation capture RX

First order kinetics: rate = k [RX] First order kinetics: rate = k [RX] unimolecular rate-determining step Carbocation intermediate Carbocation intermediate rate follows carbocation stability rearrangements are observed Reaction is not stereospecific: Reaction is not stereospecific: racemization in reactions of optically active alkyl halides Characteristics of the S N 1 mechanism

Reaction Coordinate Diagram for an S N 1 Reaction

Carbocation Stability and S N 1 Reaction Rates

The rate of nucleophilic substitution by the S N 1 mechanism is governed by electronic effects. Carbocation formation is rate-determining. The more stable the carbocation, the faster its rate of formation, and the greater the rate of unimolecular nucleophilic substitution. Electronic Effects Govern S N 1 Rates

RBr solvolysis in aqueous formic acid Alkyl bromideClassRelative rate CH 3 BrMethyl1 CH 3 CH 2 BrPrimary2 (CH 3 ) 2 CHBrSecondary43 (CH 3 ) 3 CBrTertiary100,000,000 Reactivity toward substitution by the S N 1 mechanism

CH 3 Br CH 3 CH 2 Br (CH 3 ) 2 CHBr (CH 3 ) 3 CBr Decreasing S N 1 Reactivity

Stereochemistry of S N 1 Reactions

Nucleophilic substitutions that exhibit first-order kinetic behavior are not stereospecific. Generalization

R-(–)-2-Bromooctane HC CH 3 Br CH 3 (CH 2 ) 5 (R)-(–)-2-Octanol (17%) HC CH 3 OH CH 3 (CH 2 ) 5 C H CH 3 HO (CH 2 ) 5 CH 3 (S)-(+)-2-Octanol (83%) H2OH2OH2OH2O Stereochemistry of an S N 1 Reaction

The carbocation reaction intermediate leads to the formation of two stereoisomeric products

Ionization step gives carbocation; three bonds to stereogenic center become coplanar + Step 1

Leaving group shields one face of carbocation; nucleophile attacks faster at opposite face. + Step 2

More than 50% Less than 50% +

Carbocation Rearrangements in S N 1 Reactions

carbocations are intermediates in S N 1 reactions, rearrangements are possible. Because...

Carbocations

Carbocations rearrange to the more stable form(s)

Carbocation Rearrangement Mechanism What is the starting carbocation: 1 o, 2 o or 3 o ? What is the rearranged carbocation: 1 o, 2 o or 3 o ?

Carbocation Rearrangement

CH 3 C H CHCH 3 Br CH 3 H2OH2OH2OH2O C OH CH 2 CH 3 CH 3 (93%) Example

C H CHCH 3 CH 3 C CHCH 3 CH 3 C H CHCH 3 Br CH 3 H2OH2OH2OH2O C OH CH 2 CH 3 CH 3 (93%) + H + Example

Mechanism Summary S N 1 and S N 2

When... primary alkyl halides undergo nucleophilic substitution, they always react by the S N 2 mechanism tertiary alkyl halides undergo nucleophilic substitution, they always react by the S N 1 mechanism secondary alkyl halides undergo nucleophilic substitution, they react by the S N 1 mechanism in the presence of a weak nucleophile (solvolysis) S N 2 mechanism in the presence of a good nucleophile

Putting things together