SN1 Reactions

t-Butyl bromide undergoes solvolysis when boiled in methanol:

Solvolysis: “cleavage by solvent” nucleophilic substitution reaction in

which the solvent serves as the nucleophile

CH3CCH3

CH3

Br

+ CH3OH

CH3CCH3

CH3

OCH3

+ HBr

SN1 Reactions

The reaction between t-BuBr and methanol does NOT occur via an SN2 mechanism because:

t-BuBr: tertiary alkyl halide

too hindered to be SN2 substrate

CH3OH: weak nucleophile

Solvolysis reactions occur via an SN1 mechanism:

SN1 Reactions

SN1 Reactions substitution nucleophilic unimolecular

Rate = k[R-X]1st order overall

1st order in [R-X]zero order in [Nuc]

Only R-X is present in the transition state for the rate determining stepNucleophile is NOT present in RDS

SN1 Reactions

General Mechanism:

Step 1: Formation of carbocation is the RDS.

Step 2: Attack of the nucleophile

R C

R"

R'

X R C

R"

R'

X

+ NucR C

R"

R'

R C

R"

R'

Nuc

SN1 Reactions

Reaction Energy Diagram for SN1 Reactions:

Formation of a carbocation is highly endothermic.According to Hammond’s Postulate, the transition state most closely resembles the carbocation.

SN1 Reactions

The reactivity of a substrate in an SN1 reaction depends on the stability of the carbocation formed:

3o > 2o > 1o > methyl

Allylic and benzylic halides often undergo SN1 reactions because the resulting carbocations are resonance stabilized.

CH

CH

H CH2 Br

HC

HC

H

HC

HC

H

CH2 Br

CH

HH

CH

CH

C H

H

CH

CH

H CH2 Br

HC

HC

H

HC

HC

H

CH2 Br

CH

HH

CH

CH

C H

H

+

+

SN1 Reactions

SN1 reactions involve: weak nucleophile

H2O not OH-

CH3OH not CH3O-

Substrates that form stable carbocation intermediates:3o, benzylic, or allylic halide are most favored

2o (sometimes)

SN1 Reactions

Example: Draw the mechanism for the reaction of t-butyl bromide with methanol.

SN1 Reactions

SN1 Reactions-Stereochemistry

The carbocation ion intermediate formed during an SN1 reaction is sp2 hybridized and planar. The nucleophile can attack from either side of

the carbocation.A mixture of both possible enantiomers forms.

SN1 reactions occur with racemization: a process that gives both enantiomers (not

necessarily in equal amounts) of the productRacemization occurs because both retention and inversion of configuration take place.

SN1 Reactions-Stereochemistry

CH3

C

OCH2CH

3

CH(CH3)

2

CH2CH

3

CH3

C

CH(CH3)

2

CH2CH

3

OCH2CH

3

CCH

2CH

3

CH(CH3)

2CH3 C

CH2CH

3

CH(CH3)

2CH3

+

C

CH3CH

2OH

CH2CH

3

CH(CH3)

2CH3

C

CH3CH

2OH

CH2CH

3

CH(CH3)

2CH3

Attack from top

Attack from bottom

- H+

- H+

SN1 Reactions-Stereochemistry

When the nucleophile attacks from the side where the leaving group was originally, retention of configuration occurs.

CH3

CH3

CH3

C

CH(CH3)

2

CH2CH

3

C

Br

CH(CH3)

2

CH2CH

3

C

CH2CH

3

CH(CH3)

2

OCH2CH

3

OCH2CH

3

CH3

CH3

CH3

C

CH(CH3)

2

CH2CH

3

C

Br

CH(CH3)

2

CH2CH

3

C

CH2CH

3

CH(CH3)

2

OCH2CH

3

OCH2CH

3

NaOCH2CH3

Attack from top

(R)(R)

SN1 Reactions-Stereochemistry

When the nucleophile attacks from the back side (opposite to the original leaving group), inversion of configuration occurs.

CH3

CH3

CH3

C

CH(CH3)

2

CH2CH

3

C

Br

CH(CH3)

2

CH2CH

3

C

CH2CH

3

CH(CH3)

2

OCH2CH

3

OCH2CH

3

CH3

CH3

CH3

C

CH(CH3)

2

CH2CH

3

C

Br

CH(CH3)

2

CH2CH

3

C

CH2CH

3

CH(CH3)

2

OCH2CH

3

OCH2CH

3

(R) (S)

NaOCH2CH3

Attack from bottom

SN1 Reactions-Stereochemistry

For most SN1 reactions, the leaving group partially blocks the front side of the carbonium ion more inversion of configuration less retention of configuration

SN1 Reactions-Rearrangements

Carbocations often undergo rearrangements, forming more stable cations. Structural changes resulting in a new

bonding sequence within the molecule

The driving force for a rearrangement is the formation of a more stable intermediate. 1o or 2o carbocation rearranges to a

more stable 3o carbocation or resonance-stabilized carbocation

SN1 Reactions-Rearrangements

A mixture of products often forms as a result of rearrangements during SN1 reactions. NOTE: Rearrangements cannot occur

during SN2 reactions since an intermediate is not formed.

CH3CHCHCH

3

CH3CH

2CCH

3

CH3CHCHCH

3

Br

CH3

CH3

CH3

OCH2CH

3

OCH2CH

3CH3CHCHCH

3

CH3CH

2CCH

3

CH3CHCHCH

3

Br

CH3

CH3

CH3

OCH2CH

3

OCH2CH

3

CH3CHCHCH

3

CH3CH

2CCH

3

CH3CHCHCH

3

Br

CH3

CH3

CH3

OCH2CH

3

OCH2CH

3

+CH3CH2OH

Rearranged productRearrangement occurs via

hydride shift.

SN1 Reactions-Rearrangements

Common rearrangements: Hydride shift (~H)

the movement of a hydrogen atom and its bonding pair of electrons

Methyl shift (~CH3)the movement of a methyl group and its bonding pair of electrons

Alkyl shift (~R)the movement of any alkyl group and its bonding pair of electrons

SN1 Reactions-Rearrangements

Hydride Shift Mechanism: Step 1: Formation of carbocation and

rearrangement:

CH3CHCCH

3 CH3CH

2CCH

3

CH3CHCHCH

3

CH3 CH

3

CH3

Br

CH3 CH

3

CH3

OCH2CH

3OCH

2CH

3H

C C CH3

Br H

H CH3

C

H

C CH3

H

CH3

C

H

C CH3

CH3

H

CH3CHCCH

3 CH3CH

2CCH

3

CH3CHCHCH

3

CH3 CH

3

CH3

Br

CH3 CH

3

CH3

OCH2CH

3OCH

2CH

3H

C C CH3

Br H

H CH3

C

H

C CH3

H

CH3

C

H

C CH3

CH3

H

+

CH3CHCCH

3 CH3CH

2CCH

3

CH3CHCHCH

3

CH3 CH

3

CH3

Br

CH3 CH

3

CH3

OCH2CH

3OCH

2CH

3H

C C CH3

Br H

H CH3

C

H

C CH3

H

CH3

C

H

C CH3

CH3

H+

+ Br -

~H2o

3o

SN1 Reactions-Rearrangements

Hydride Shift Mechanism: Step 2: Nucleophile attack and loss of

proton (if needed)

CH3CHCCH

3 CH3CH

2CCH

3

CH3CHCHCH

3

CH3 CH

3

CH3

Br

CH3 CH

3

CH3

OCH2CH

3OCH

2CH

3H

C C CH3

Br H

H CH3

C

H

C CH3

H

CH3

C

H

C CH3

CH3

H OCH2CH

3

H

CH3CHCCH

3 CH3CH

2CCH

3

CH3CHCHCH

3

CH3 CH

3

CH3

CH3

CH3

Br

CH3 CH

3

CH3

OCH2CH

3OCH

2CH

3H

C C CH3

Br H

H CH3

C

H

C CH3

H

CH3

C

H

C CH3

CH3

H OCH2CH

3

H

C

H

H

C CH3

CH3

OCH2CH

3

H

C

H

H

C CH3

CH3

OCH2CH

3

CH3CHCCH

3 CH3CH

2CCH

3

CH3CHCHCH

3

CH3 CH

3

CH3

CH3

CH3

Br

CH3 CH

3

CH3

OCH2CH

3OCH

2CH

3H

C C CH3

Br H

H CH3

C

H

C CH3

H

CH3

C

H

C CH3

CH3

H

C

H

H

C CH3

CH3

OCH2CH

3

H

C

H

H

C CH3

CH3

OCH2CH

3

+ CH3CH2OH+

CH3CH2OHCH3CH2OH2

+ +

SN1 Reactions-Rearrangements

Example of a Methyl Shift (~CH3):

CH3CCH2Br

CH3

CH3

EtOH

CH3CCH2OCH2CH3

CH3

CH3

CH3CCH2CH3

OCH2CH3

CH3EtOH

CH3CCH2Br

CH3

CH3

SN1 Reactions-Rearrangements

Mechanism of ~CH3: Step 1: Simultaneous (because primary

carbocation is unstable) shift of methyl group and loss of leaving group:

3o carbocation formed preferentially

CH3C

CH3

CH3

C

H

H

Br~CH3 CH3CCH2CH3

CH3

+ Br-

SN1 Reactions-Rearrangements

Mechanism of ~CH3: Step 2: Attack of nucleophile and loss

of proton (if needed)

CH3CCH2CH3

CH3 CH3CH2OHCH3CCH2CH3

CH3

CH3CH2OH

CH3CH2OHCH3CCH2CH3

CH3

OCH2CH3

CH3CH2OH2+ +

Important! Important! Important!

How do you know if the carbocation forms first and then rearrangement occurs or if formation of carbocation and rearrangement occur simulataneously???

In general: Secondary (2o) halides form the carbocation first and then rearrangement occurs (i.e. 2 steps)

In general: Primary halides undergo simultaneous formation of carbocation and rearrangement. (Primary carbocation is quite unstable!)

SN1 Reactions-Rearrangements

Example: Propose a mechanism for the following reaction.

CH3

Cl

CH3

OCH2CH

3

CH3

OCH2CH

3

CH3

Cl

CH3

OCH2CH

3

CH3

OCH2CH

3

CH3

Cl

CH3

OCH2CH

3

CH3

OCH2CH

3

CH2CH3OH

+

SN1 vs. SN2

SN2

Strong nucleophile

Primary or methyl halide

Polar aprotic solvents (acetone, CH3CN, DMF)

Inversion at chiral carbon

No rearrangements

Weak nucleophile (may also be solvent)

Tertiary,allylic, benzylic halides

Polar protic solvent (alcohols, water)

Racemization of optically active compound

Rearranged products

SN1

E1 Reactions

An elimination reaction involves the loss of two atoms or groups of atoms from a substrate, usually forming a new bond.

Elimination reactions can occur via a first order (E1) or a second order (E2) process.

H

C

C C

H

CH3 Br

CH2CH

3

CH2CH

3

CH

3C

H CH2CH

3

CH2CH

3

H

C

C C

H

CH3 Br

CH2CH

3

CH2CH

3

CH

3C

H CH2CH

3

CH2CH

3

Na+ -OCH3

CH3OH

+ Br -

E1 Reactions

E1 reactions: Elimination, unimolecular

1st order kineticsRate = k[R-X]RDS transition state involves a single molecule

General conditions:3o and 2o halidesweak bases

E1 ReactionsE1 Mechanism:Step 1: Formation of carbocation (RDS)

Step 2: Base abstracts proton

C C

R""

X

R'

R

R"

H

C C

R""

R'

R

R"

H

X

C C

R""

R'

R

R"

H

B C C

R""

R

R"

R'H B

cis and trans

E1 Reactions

E1 reactions almost always occur together with SN1 reactions.

CH3CCH3

CH3

Br

EtOH H2C C

CH3

CH3

(E1)

+

CH3CCH3

CH3

OCH2CH3

(SN1)

E1 Reactions

CH3CH2-O-H

H

+

E1 Reactions

Once formed, a carbonium ion can: recombine with the leaving group react with a nucleophile forming a

substitution product (SN1) lose a proton to form an alkene (E1) rearrange to form a more stable

carbocation and then:react with nucleophilelose a proton to form an alkene

E2 Reactions

E2 reactions: Elimination, bimolecular

2nd order kineticsRate = k[R-X][B-]RDS transition state involves two molecules

General conditions:3o and 2o halidesstrong bases

E2 Reactions In the presence of a strong base,

elimination generally occurs in a concerted reaction via an E2 mechanism

B -

E2 Reactions

SN2 reactions require an unhindered methyl or 1o halide steric hinderance prevents nucleophile

from attacking 3o halides and forming the substitution product

E2 reactions generally involve the reaction between a 3o and 2o alkyl halides and a strong base.

E2 Reactions The reaction of t-butyl bromide with methoxide

ion gives only the elimination product.

The base attacks the alkyl bromide much faster than the bromide can ionize.

E2 Reactions

Many alkyl halides can eliminate in more than one way. Mixture of alkenes produced

E2 Reactions

Saytzeff Rule: When two or more elimination products

can be formed, the product with the most highly substituted double bond will usually predominate.

R2C=CR2 > R2C=CHR > RHC=CHR and R2C=CH2 > RHC=CH2

E2 Reactions

Example: Draw the structures for all possible products of the following reaction. Which one will predominate?

Br CH3

NaOCH2CH3

EtOH

E2 Reactions

E2 reactions follow a concerted mechanism: bonds breaking and forming

simultaneously

specific geometry required to allow overlap of orbitals of bonds being broken and bonds being formed

E2 reactions commonly involve an anti-coplanar conformation.

E2 Reactions

E2 Reactions

Example: Predict the structure of the elimination product formed by the following reaction.

C C

HBr

H

CH3

PhPh

NaOCH3

CH3OH

C

C

Ph =

C

H

CH3

PhBr

HPh

CPh

H

CH3

Ph

E1 vs E2

E1

Weak base 30 > 2o Good ionizing

solvent polar, protic

(water, alcohols)

Saytzeff product No required

geometry

Rearranged products possible

Strong base required

3o > 2o

Solvent polarity not important

Saytzeff product Coplanar leaving

groups (usually anti) No rearrangements

E2