Nucleophilic Substitution Reactions:

SN1 Mechanism

Two Step MechanismWhich step is rate determining?

A) Step #1 B) Step #2

Tertiary alkyl halides are very unreactive in substitutions that proceed by the SN2 mechanism.

But they are highly reactive in solvolysis reactions where the solvent is generally one of the reactants.

Solvolysis Reactions

Hydrolysis of tert-butyl bromide.

+

+

H Br..

..:

O: :

H

H

C

CH3

CH3

CH3

Br

C OH..

..

..

.. :

CH3

CH3

CH3

C+

+

O :

H

H

Br..

..::–

CH3

CH3

CH3

+ O: :

H

H

C+

+

O :

H

H

Br..

..::–

CH3

CH3

CH3

C

CH3

CH3

CH3

Br..

.. :

This is the nucleophilic substitutionstage of the reaction; the one withwhich we are concerned.

Hydrolysis of tert-butyl bromide.

+ O: :

H

H

C+

+

O :

H

H

Br..

..::–

CH3

CH3

CH3

C

CH3

CH3

CH3

Br..

.. :

The reaction rate is independentof the concentration of the nucleophileand follows a first-order rate law.

rate = k[(CH3)3CBr]

Hydrolysis of tert-butyl bromide.

+ O: :

H

H

+

Br..

..::–

C+O :

H

HCH3

CH3

CH3

C

CH3

CH3

CH3

Br..

.. :

The mechanism of this step isnot SN2. It is called SN1 and begins with ionization of (CH3)3CBr.

Hydrolysis of tert-butyl bromide.

rate = k[alkyl halide]First-order kinetics implies a unimolecular

rate-determining step.

Proposed mechanism is called SN1, which stands for

substitution nucleophilic unimolecular

Kinetics and Mechanism

+ Br–

..: :

..

C

CH3

CH3

CH3

Br..

.. :

C

H3C CH3

CH3

+

unimolecular slow

Mechanism

C

H3C CH3

CH3

+

O: :

H

H

C+O :

H

HCH3

CH3

CH3

Mechanism

bimolecular fast

ROH2

+

carbocation formation

R+

proton transfer

ROH

carbocation capture

RX

first order kinetics: rate = k[RX]

unimolecular rate-determining step

carbocation intermediate

rate follows carbocation stability

rearrangements sometimes observed

reaction is not stereospecific

racemization occurs in reactions of optically active alkyl halides

Characteristics of the SN1 mechanism

Question

What is the rate-determining step in the reaction of cyclobutanol with HCl?

A) protonation of the OH group

B) attack of the bromide on the carbocation

C) simultaneous formation of the C-Br bond and the breaking of the C-OH bond

D) carbocation formation

The species shown below represents _____ of the reaction between isopropyl alcohol andhydrogen bromide.

A) the alkyloxonium ion intermediateB) the transition step of the bimolecular

proton transferC) the transition state of the attack of the

nucleophile on the carbocationD) the transition state of the unimolecular

dissociation

Question

Carbocation Stability and SN1

Reaction Rates

The rate of nucleophilic substitutionby the SN1 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 SN1 Rates

RBr solvolysis in aqueous formic acid

Alkyl bromide ClassRelative rate

CH3Br Methyl 1

CH3CH2Br Primary 2

(CH3)2CHBr Secondary 43

(CH3)3CBr Tertiary 100,000,000

Reactivity toward substitution by the SN1 mechanism

CH3Br

CH3CH2Br

(CH3)2CHBr

(CH3)3CBr

Decreasing SN1 Reactivity

Question

Select the most stable carbocation.

A) B)

C) D)

Question

Which one of the following reacts with HBr at the fastest rate?

A) B)

C) D)

Stereochemistry of SN1 Reactions

Nucleophilic substitutions that exhibitfirst-order kinetic behavior are

not stereospecific.

Generalization

R-(–)-2-Bromooctane

H

C

CH3

Br

CH3(CH2)5

Stereochemistry of an SN1 Reaction

(R)-(–)-2-Octanol (17%)

H

C

CH3

OH

CH3(CH2)5

C

H CH3

HO

(CH2)5CH3

(S)-(+)-2-Octanol (83%)

H2O

Leaving group shields

one face of carbocation;

nucleophile attacks

faster at opposite face.

+

Figure

Ionization step

gives carbocation; three

bonds to chirality

center become coplanar

Structure of tert-Butyl Cation

Positively charged carbon is sp2 hybridized.

All four carbons lie in same plane.

Unhybridized p orbital is perpendicular to plane of four carbons.

C

CH3

H3C

CH3

+

More than 50% Less than 50%

+

Carbocation Capture

+

Cl–

Lewis acid Lewis base

Electrophile Nucleophile

C

CH3

CH3H3C

+ C

H3C

CH3H3C

Cl

Carbocation Rearrangements

in SN1 Reactions

carbocations are intermediatesin SN1 reactions, rearrangements

are possible.

Because...

CH3 C

H

CHCH3

Br

CH3H2O

CH3 C

OH

CH2CH3

CH3

(93%)

Example

CH3 C

H

CHCH3

CH3

+

H2O

CH3 C CHCH3

CH3

H

+

Effect of Solventon the

Rate of Nucleophilic Substitution

SN1 Reaction Rates Increase

in Polar Solvents

In general...

Solvent Dielectric Relative constant rate

acetic acidmethanolformic acidwater

SN1 Reactivity versus Solvent Polarity

Most polar Fastest rate

R+

RX

R X

energy of RX not much affected by polarity of solvent

transition state stabilized by polar solvent

R+

RX

R X

energy of RX not much affected by polarity of solvent

transition state stabilized by polar solvent

activation energy decreases;

rate increases

SN2 Reaction Rates Increase in

Polar Aprotic Solvents

An aprotic solvent is one that doesnot have an —OH group.

In general...

Solvent Type Relative Rate

CH3OH polar protic 1

H2O polar protic 7

DMSO polar aprotic 1300

DMF polar aprotic2800

Acetonitrile polar aprotic 5000

CH3CH2CH2CH2Br + N3–

SN2 Reactivity versus Type of Solvent

Mechanism SummarySN1 and SN2

When...

primary alkyl halides undergo nucleophilic substitution, they always react by the SN2

mechanism

tertiary alkyl halides undergo nucleophilic substitution, they always react by the SN1

mechanism

secondary alkyl halides undergo nucleophilic substitution, they react by the

SN1 mechanism in the presence of a weak nucleophile (solvolysis)SN2 mechanism in the presence of a good nucleophile

The most commonly used leaving groups are halides and sulfonate ions.

CONCEPTUAL CHECKPOINT 7.28.

SN1 vs. SN2 – The Leaving Group

To promote an SN1 reaction, use a polar, protic solvent: The protic solvent will hydrogen bond with the nucleophile, stabilizing it, while the leaving group leaves first.

SN2 vs. SN1 – Solvent

SN2 reaction, use a polar, aprotic solvent

Various Functions from Substitution Reactions

Calibrated Peer Review / Lab Experimentation

http://chemconnections.org/organic/chem226/calendar-f-12