Unimolecular Nucleophilic Substitution S N 1 A question

Unimolecular Nucleophilic Substitution S N 1

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

The Sn 1 Reaction

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

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

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

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

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

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

Reaction Coordinate Diagram for an SN 1 Reaction

Carbocation Stability and SN 1 Reaction Rates

Electronic Effects Govern SN 1 Rates The rate of nucleophilic substitution by the SN 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.

Reactivity toward substitution by the SN 1 mechanism RBr solvolysis in aqueous formic acid Alkyl bromide Class CH 3 Br Methyl CH 3 CH 2 Br. Primary (CH 3)2 CHBr Relative rate 1 2 Secondary (CH 3)3 CBr Tertiary 43 100, 000

Decreasing SN 1 Reactivity (CH 3)3 CBr (CH 3)2 CHBr CH 3 CH 2 Br CH 3 Br

Stereochemistry of SN 1 Reactions

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

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

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

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

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

+ More than 50% Less than 50%

Carbocation Rearrangements in SN 1 Reactions

Because. . . carbocations are intermediates in SN 1 reactions, rearrangements are possible.

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

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

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

Mechanism Summary SN 1 and SN 2

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

Putting things together