Unimolecular Nucleophilic SubstitutionUnimolecular Nucleophilic SubstitutionSSNN11

Tertiary alkyl halides are very unreactive in Tertiary alkyl halides are very unreactive in substitutions that proceed by the Ssubstitutions that proceed by the SNN2 mechanism.2 mechanism.Do they undergo nucleophilic substitution at all?Do they undergo nucleophilic substitution at all?

Yes. But by a mechanism different from SYes. But by a mechanism different from SNN2. 2. The most common examples are seen in The most common examples are seen in solvolysis reactions.solvolysis reactions.

A question...A question...

The Sn1 ReactionThe Sn1 Reaction

++

++

HH BrBr........ ::

OO:: ::

HH

HH

CCCHCH33

CHCH33

CHCH33

BrBr

CC OHOH........

....

.... ::

CHCH33

CHCH33

CHCH33

Example of a solvolysis. Hydrolysis of Example of a solvolysis. Hydrolysis of terttert-butyl bromide.-butyl bromide.

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

rate-determining step.rate-determining step.

Mechanism is called SMechanism is called SNN1, which stands for1, which stands forsubstitution nucleophilic unimolecular (1)substitution nucleophilic unimolecular (1)

Kinetics and MechanismKinetics and Mechanism

++ BrBr––

....:: ::

....

unimolecular unimolecular slowslow

CCCHCH33

CHCH33

CHCH33

BrBr........ ::

CC

HH33CC CHCH33

CHCH33

++

MechanismMechanism

bimolecular bimolecular fastfast

CC

HH33CC CHCH33

CHCH33

++

OO:: ::

HH

HH

CC++OO ::

HH

HHCHCH33

CHCH33

CHCH33

MechanismMechanism

proton transfer

ROHROH22

++

carbocation formation

RR++

ROHROH

carbocation capture

RXRX

• First order kinetics: rate = k [RX]First order kinetics: rate = k [RX]unimolecular rate-determining stepunimolecular rate-determining step

• Carbocation intermediateCarbocation intermediaterate follows carbocation stabilityrate follows carbocation stabilityrearrangements are observedrearrangements are observed

• Reaction is not stereospecific:Reaction is not stereospecific:racemization in reactions of racemization in reactions of optically active alkyl halidesoptically active alkyl halides

Characteristics of the SCharacteristics of the SNN1 mechanism1 mechanism

Reaction Coordinate Diagram for an SN1 Reaction

Carbocation Stability and SCarbocation Stability and SNN1 Reaction 1 Reaction RatesRates

The rate of nucleophilic substitutionThe rate of nucleophilic substitutionby the Sby the SNN1 mechanism is governed1 mechanism is governed

by electronic effects.by electronic effects.

Carbocation formation is rate-determining.Carbocation formation is rate-determining.The more stable the carbocation, the fasterThe more stable the carbocation, the faster

its rate of formation, and the greater the its rate of formation, and the greater the rate of unimolecular nucleophilic substitution.rate of unimolecular nucleophilic substitution.

Electronic Effects Govern SElectronic Effects Govern SNN1 Rates1 Rates

RBr solvolysis in aqueous formic acidRBr solvolysis in aqueous formic acid

Alkyl bromideAlkyl bromide ClassClass Relative rateRelative rate

CHCH33BrBr MethylMethyl 11

CHCH33CHCH22BrBr PrimaryPrimary 22

(CH(CH33))22CHBrCHBr SecondarySecondary 4343

(CH(CH33))33CBrCBr TertiaryTertiary 100,000,000100,000,000

Reactivity toward substitution by the SReactivity toward substitution by the SNN1 1 mechanismmechanism

CHCH33BrBr

CHCH33CHCH22BrBr

(CH(CH33))22CHBrCHBr

(CH(CH33))33CBrCBr

Decreasing SDecreasing SNN1 Reactivity1 Reactivity

Stereochemistry of SStereochemistry of SNN1 Reactions1 Reactions

Nucleophilic substitutions that exhibitNucleophilic substitutions that exhibitfirst-order kinetic behavior are first-order kinetic behavior are

not stereospecific.not stereospecific.

GeneralizationGeneralization

RR-(–)-2-Bromooctane-(–)-2-Bromooctane

HH

CC

CHCH33

BrBr

CHCH33(CH(CH22))55

((RR)-(–)-2-Octanol (17%))-(–)-2-Octanol (17%)

HH

CC

CHCH33

OHOH

CHCH33(CH(CH22))55

CC

HH CHCH33

HOHO

(CH(CH22))55CHCH33

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

HH22OO

Stereochemistry of an SStereochemistry of an SNN1 Reaction1 Reaction

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

Ionization stepIonization stepgives carbocation; threegives carbocation; threebonds to stereogenicbonds to stereogeniccenter become coplanarcenter become coplanar

++

Step 1Step 1

Leaving group shieldsLeaving group shieldsone face of carbocation;one face of carbocation;nucleophile attacks nucleophile attacks faster at opposite face.faster at opposite face.

++

Step 2Step 2

More than 50%More than 50% Less than 50%Less than 50%

++

Carbocation RearrangementsCarbocation Rearrangementsin Sin SNN1 Reactions1 Reactions

carbocations are intermediatescarbocations are intermediatesin Sin SNN1 reactions, rearrangements1 reactions, rearrangements

are possible.are possible.

Because...Because...

CarbocationsCarbocations

Carbocations rearrange to Carbocations rearrange to the more stable form(s)the more stable form(s)

Carbocation Rearrangement Carbocation Rearrangement MechanismMechanism

What is the starting carbocation: 1What is the starting carbocation: 1oo, 2, 2oo or 3 or 3oo??What is the rearranged carbocation: 1What is the rearranged carbocation: 1oo, 2, 2oo or 3 or 3oo??

Carbocation RearrangementCarbocation Rearrangement

CHCH33 CC

HH

CHCHCHCH33

BrBr

CHCH33 HH22OOCHCH33 CC

OHOH

CHCH22CHCH33

CHCH33

(93%)(93%)

ExampleExample

CHCH33 CC

HH

CHCHCHCH33

CHCH33

CHCH33 CC CHCHCHCH33

CHCH33

CHCH33 CC

HH

CHCHCHCH33

BrBr

CHCH33

HH22OO

CHCH33 CC

OHOH

CHCH22CHCH33

CHCH33

(93%)(93%)

++HH

++

ExampleExample

Mechanism SummaryMechanism SummarySSNN1 and S1 and SNN22

When...When...

primaryprimary alkyl halides undergo nucleophilic alkyl halides undergo nucleophilic substitution, they substitution, they alwaysalways react by the react by the SSNN2 2 mechanismmechanism

tertiarytertiary alkyl halides undergo nucleophilic alkyl halides undergo nucleophilic substitution, they substitution, they alwaysalways react by the react by the SSNN1 1 mechanismmechanism

secondarysecondary alkyl halides undergo nucleophilic alkyl halides undergo nucleophilic substitution, they react by thesubstitution, they react by the

SSNN11 mechanism in the presence of a weak mechanism in the presence of a weak nucleophile (solvolysis)nucleophile (solvolysis)SSNN22 mechanism in the presence of a good mechanism in the presence of a good nucleophilenucleophile

Putting things togetherPutting things together