SN1 mechanisms always proceed via a carbocation intermediate in the rate determining step. The nucleophile then quickly attacks the carbocation to form the products:

Recall that the following reaction does not proceed via an SN2 mechanism. The electrophilic carbon atom is too sterically crowded for the nucleophile to attack it. For this type of substrate, the reaction proceeds by a different mechanism, an SN1 mechanism.

Substitution Reactions – SN1

I (H3C)3C Br C(CH3)3I Br+ +

1

There may be more steps depending on the electrophile and/or nucleophile.

Reactions in which the solvent participates as the nucleophile are known as solvolysis reactions.

(H3C)3C Br Br+H2O (H3C)3C OH + H +

Substitution Reactions – SN1

2

Sketch a reaction profile diagram for the following reaction:

Substitution Reactions – SN1

I (H3C)3C Br C(CH3)3I Br+ +

3

Substitution Reactions – SN1

SN1 reactions predominate when:•A relatively stable carbocation is formed.•The solvent is polar and protic.•The nucleophile is a weak base (preferably a neutral molecule like H2O, ROH, etc.).

Carbocation Stability

Carbocation stability is dependent on:•Delocalization (resonance).•Hyperconjugation.

4

Carbocation Stability – Resonance Delocalization

We have already seen how a delocalized charge is more stable than a localized one. For each of the following molecules, form the carbocation and draw all reasonable resonance structures:

C C

H

H H2C

H

Br

H3CO

H2C

Cl

CH2 Cl

5

Note that aryl and vinyl carbocations cannot be stabilized by resonance. The empty p-orbital is orthogonal to the π-system and as such cannot be delocalized:

CH

H

H

H

H

C

Carbocation Stability – Resonance Delocalization

6

Carbocations can also be stabilized by inductive effects. That is, electron rich groups can donate electron density through the sigma bonds to help stabilize a carbocation:

Carbocation Stability – Inductive effects and Hyperconjugation

Inductive effects are enhanced by hyperconjugation, a phenomenon where electron rich sigma MOs overlap with the empty p-orbital of the carbocation.

7

Just as aryl and vinyl carbocations are not stabilized by resonance, they are also not stabilized by hyperconjugation:

Carbocation Stability

Considering these effects, we can arrange the different types of carbocations on the :

3 w/ resonance3 w/out resonance

or2 w/ resonance

2 w/out resonanceor

1 w/ resonance

1 w/out resonance methylvinyl

oraryl>> > > >>

The type of carbon atoms highlighted in red do not form carbocations in most cases

8

One consequence of reactions proceeding via carbocation intermediates is the occurrence of rearrangement side reactions. Consider the following reaction:

The substitution product is a constitutional isomer of the product expected. Propose a mechanism for the above reaction:

SN1 - Rearrangements

H H

CH3

Br H

H+ Br–OH

H HH

CH3

HOH

+++

9

It is worth noting that carbocation rearrangements can involve shifting either a hydride ion or a methyl anion. In either case, you will always be forming a more stable carbocation.

SN1 - Rearrangements

Pay close attention to the way curly arrows are drawn when proposing a hydride or methyl shift. We should be able to tell if you’re proposing a hydride shift or generation of a pi bond.

10

The SN1 Reaction - Kinetics.

•What happens to the rate of production of (CH3)3CI if the concentration of I- is held constant and the concentration of (CH3)3CBr is increased?

Consider:

•What happens to the rate of production of (CH3)3CI if the concentration of (CH3)3CBr is held constant and the concentration of I- is increased?

I - + (CH3)3CBr → (CH3)3CI + Br -

11

As we did for the SN2 reaction, we can also write a rate law for the SN1 reaction:

The SN1 Reaction - Kinetics.

I - + (CH3)3CBr → (CH3)3CI + Br -

Again, as with the SN2 reaction, this type of graph is not that useful since we cannot predict the rate of reaction at some future time. In order to do so we would need to convert the graph into a linear function which is outside the scope of this course.

Considering what happens to the concentrations of reactants, what would a graph or reaction rate vs. time look?

12

The Stereochemistry of the SN1 reaction

Unlike in an SN2 reaction, an SN1 reaction at an asymmetric carbon generates a racemic mixture of products.

C

PhCH2CH3H3C

BrNaI/Acetone

C PhCH2CH3H3C

C

PhCH2CH3H3C

I

C

CH2CH3PhH3C

I

The nature of the intermediate is such that the nucleophile can attack from either side with equal likelihood. 13

The Stereochemistry of the SN1 reaction

C

PhCH2CH3H3C

BrNaI/Acetone

C PhCH2CH3H3C

C

PhCH2CH3H3C

I

Br-

C

CH2CH3PhH3C

I

Sometimes (depending on conditions) reactions occur with only partial racemization.

14

SN1 and SN2 reactions – Solvent Effects

SN1 reactions are typically done in polar protic solvents. Polar protic solvents are used because they help stabilize the transition state during the process of forming the carbocation intermediate. The more stabilized the transition state, the faster the carbocation will form:

Some common polar protic solvents:

H3CC

OH

OOH

CH3CH2OH CH3OH H2OOH

t-Butanol(t-BuOH) Isopropanol

(iPrOH)Ethanol(EtOH)

Methanol(MeOH)

WaterAcetic AcidAcOH

15

SN1 and SN2 reactions – Solvent Effects

SN2 reactions are typically done in polar aprotic solvents. These solvents are polar enough to solubilize the nucleophile but don’t stabilize the nucleophiles enough to prevent reaction:

Some common polar aprotic solvents:

H3CC

CH3

O

H3C C N CH3OCH2CH2OCH3

HC

N(CH3)2

O

H3CS

CH3

O

H3CH2CO

CH2CH3

N

O

AcetoneAcetonitrile

(MeCN)Dimethoxyethane

(DME) Dimethylformamide(DMF)

Dimethyl sulfoxide(DMSO)

Ethyl ether(Et2O) Pyridine

(Pyr)Tetrahydrof uran

(THF) 16

SN1 vs. SN2 reactions – Comparison

Minimum # Steps 1 or more steps 2 or more steps

Intermediates? not necessarily carbocation

Reaction Order second order reaction first order reaction

Stereochemical stereospecific inversion of racemization (full or partial)Consequences configuration at electrophilic site at electrophilic site

Importance of very important; no reaction unimportantNucleophile Strength for weak nucleophiles like H2O

Importance of very important; no reaction for very important; no reaction forLeaving Group weak leaving groups like HO- weak leaving groups like HO-

Substrate Structure avoid steric hindrance; need carbocation stabilization;Dependence CH3 > 1 > 2(slow) > 3 (no); 3 > 2 (slow) > 1 (no);

no reaction for aryl/vinyl resonance stabilization helps;no reaction for aryl/vinyl

Solvent polar aprotic polar protic

Competing Reactions E2 E1, E2, rearrangement

SN1SN2

17

NaIacetone

Cl+

N a Ia c e t o n e

Cl+

Ag+

ClOH + + Ag+

ClOH + +

ClBr

– +

ClO

H

H+

SN1 vs. SN2 reactions

Would you expect the following reactions to proceed via SN1, SN2, both, or neither ? Draw the expected product(s) for each reaction.

18