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
CH3 CCH3
CH3
Br + CH3OH CH3 CCH3
CH3
OCH3 + HBr
SN1 Reactions
The reaction between t-BuBr and methanol does NOT occur via an SN2 mechanism because: t-BuBr:
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 step
Nucleophile is NOT present in RDS
SN1 Reactions General Mechanism:
Step 1:
R X R+ + X-
Step 2:
R+ + Nuc - R Nuc
Rate determining step
SN1 Reactions
Reaction Energy Diagram for SN1 Reactions:Formation of carbonium ion is highly endothermic
According to Hammond’s Postulate, the transition state most closely resembles the carbonium ion.
SN1 Reactions
The reactivity of a substrate in an SN1 reaction depends on the stability of the carbonium ion formed:
3o > 2o > 1o > methyl
Allylic and benzylic halides undergo SN1 reactions because the resulting carbonium ions are resonance stabilized.
CH
CH
H CH2 Br
HC
HC
H
HC
HC
H
CH2 Br
CH
HH
CH
CH
C HH
CH
CH
H CH2 Br
HC
HC
H
HC
HC
H
CH2 Br
CH
HH
CH
CH
C HH
++
SN1 Reactions SN1 reactions involve:
weak nucleophile H2O not OH-
CH3OH not CH3O-
Substrates that form stable carbonium ion intermediates:
3o, benzylic, or allylic halide are most favored
2o (sometimes)
SN1 Reactions
Example: Draw the mechanism for the SN1 reaction of t-butyl bromide with methanol
Step 1: Slow ionization of R-X to form carbonium ion: rate determining step
SN1 Reactions
Step 2: Fast attack of nucleophile on the carbonium
ion
SN1 Reactions
Step 3: (Not needed for all SN1 reactions) Solvent molecule removes proton, leaving
the neutral product
SN1 Reactions-Stereochemistry The carbonium ion intermediate formed during
an SN1 reaction is sp2 hybridized and planar. The nucleophile can attack from either side
of the carbonium ion. A mixture of both possible enantiomers
forms.
Racemization: a process that gives both enantiomers of
the product not necessarily in equal amounts
SN1 Reactions-Stereochemistry
CH3 COCH2CH3
CH(CH3)2CH2CH3
CH3 C
CH(CH3)2
CH2CH3
OCH2CH3
CCH2CH3
CH(CH3)2CH3 CCH2CH3
CH(CH3)2CH3+
C
CH3CH2OH
CH2CH3
CH(CH3)2CH3
C
CH3CH2OH
CH2CH3
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
CH2CH3
C
Br
CH(CH3)2
CH2CH3
C
CH2CH3
CH(CH3)2
OCH2CH3
OCH2CH3
CH3
CH3
CH3 C
CH(CH3)2
CH2CH3
C
Br
CH(CH3)2
CH2CH3
C
CH2CH3
CH(CH3)2
OCH2CH3
OCH2CH3
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
CH2CH3
C
Br
CH(CH3)2
CH2CH3
C
CH2CH3
CH(CH3)2
OCH2CH3
OCH2CH3
CH3
CH3
CH3 C
CH(CH3)2
CH2CH3
C
Br
CH(CH3)2
CH2CH3
C
CH2CH3
CH(CH3)2
OCH2CH3
OCH2CH3
(R) (S)
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
Carbonium ions 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 carbonium ion rearranges to a more
stable 3o carbonium ion or resonance-stabilized carbonium ion
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.
CH3CHCHCH3
CH3CH2CCH3
CH3CHCHCH3
Br
CH3
CH3
CH3
OCH2CH3
OCH2CH3CH3CHCHCH3
CH3CH2CCH3
CH3CHCHCH3
Br
CH3
CH3
CH3
OCH2CH3
OCH2CH3
CH3CHCHCH3
CH3CH2CCH3
CH3CHCHCH3
Br
CH3
CH3
CH3
OCH2CH3
OCH2CH3+
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
SN1 Reactions-Rearrangements
Hydride Shift Mechanism: Step 1: Formation of carbonium ion and
rearrangement:
SN1 Reactions-Rearrangements
Hydride Shift Mechanism: Step 2: Nucleophile attack and loss of
proton (if needed)
CH3
CH3
CH3
CH3
CCH3
CH3
CH2 Br
CCH3
CH3
CH2 Br
CCH3
CH2
CCH3
CH3
CH2
CH3
OCH2CH3
OCH2CH3CH3
CH3
CH3
CH3
CCH3
CH3
CH2 Br
CCH3
CH3
CH2 Br
CCH3
CH2
CCH3
CH3
CH2
CH3
EtOH
SN1 Reactions-Rearrangements
Example of a Methyl Shift (~CH3):
CH3
CH3
CH3
CH3
CCH3
CH3
CH2 Br
CCH3
CH3
CH2 Br
CCH3
CH2
CCH3
CH3
CH2
CH3
CH3
CH3
CH3
CH3
CCH3
CH3
CH2 Br
CCH3
CH3
CH2 Br
CCH3
CH2
CCH3
CH3
CH2
CH3
OCH2CH3
EtOH
SN1 Reactions-Rearrangements
Mechanism of ~CH3: Step 1: Simultaneous (often) shift of methyl
group and loss of leaving group:
SN1 Reactions-Rearrangements
Mechanism of ~CH3: Step 2: Attack of nucleophile and loss of
proton (if needed)
SN1 Reactions-Rearrangements
Example: Propose a mechanism for the following reaction.
CH3
Cl
CH3
OCH2CH3
CH3OCH2CH3
CH3
Cl
CH3
OCH2CH3
CH3OCH2CH3
CH3
Cl
CH3
OCH2CH3
CH3
OCH2CH3
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 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 CH
CH3 Br
CH2CH3
CH2CH3
CH3C
H CH2CH3
CH2CH3
H
C
C CH
CH3 Br
CH2CH3
CH2CH3
CH3C
H CH2CH3
CH2CH3
Na+ -OCH3
CH3OH
+ Br -
E1 Reactions E1 reactions:
Elimination, unimolecular
1st order kinetics Rate = k[R-X] RDS transition state involves a single
molecule
General conditions: 3o and 2o halides weak bases
E1 Reactions E1 Mechanism:
E1 Reactions E1 reactions almost always occur together
with SN1 reactions.
CH3 + CH3CH2OH
CH2 + CH3
C
CH3
Br
CH3
CCH3
CH3
C OCH2CH3
CH3
CH3
CH3 + CH3CH2OH
CH2 + CH3
C
CH3
Br
CH3
CCH3
CH3
C OCH2CH3
CH3
CH3
E1 SN1
E1 Reactions
CH3CH2-O-HH
+
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 carbonium
ion and then: react with nucleophile lose a proton to form an alkene
E2 Reactions E2 reactions:
Elimination, bimolecular
2nd order kinetics Rate = k[R-X][B-] RDS transition state involves two molecules
General conditions: 3o and 2o halides strong bases
E2 Reactions In the presence of a strong base, elimination
generally occurs in a concerted reaction via an E2 mechanism
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 ReactionsExample: Predict the structure of the elimination product formed by the following reaction.
C C
HBr
H
CH3PhPh
NaOCH3
CH3OH
C
C
Ph =
CH
CH3PhBr
HPh
CPh
H
CH3
Ph
E1 vs E2E1
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
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