Chapter 7a Lecture Slides PDF
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joseph changChapter 7 Alkyl Halides: Nucleophilic Substitution and
Elimination Reactions 1˚ halide
Hello
3˚
halide
Chapter 7 Alkyl Halides: Nucleophilic Substitution and
Elimination Reactions
Topics:
I. Introduction to Substitution and Elimination Reactions
II. Nomenclature and Uses of Alkyl Halides
III. SN2 Reactions
IV. Nucleophilic Strength and Solvent Effects in SN2 Reactions
V. Hello
SN2 Reactions in Biological Systems-Methylation
VI. Introduction to E2 Reactions
VII. Nomenclature and Stability of Alkenes
VIII. Regiochemical and Stereochemical Outcomes for E2 Reactions
IX. Unimolecular Reactions (SN1 and E1)
X. Kinetic Isotope Effects in Elimination Reactions
XI. Predicting Products: Substitution vs. Elimination
XII. Substitution and Elimination Reactions with Other Substrates
XIII. Synthesis Strategies
XIV. Building your “Toolbox” of Reactions
2
I. Introduction to Substitution and Elimination Reactions
• Substitution and Elimination reaction are two of the
most common reactions in organic chemistry!
• Alkyl halides undergo substitution and elimination rxns
Hello
Alkyl halide Aryl halide Vinyl halide
– Which structure represents an alkyl halide?
I. Introduction to Substitution and Elimination Reactions
• Alkyl Halides can undergo a substitution reaction when reacted
with a nucleophile.
Hello
• Alkyl Halides can undergo an elimination reaction when reacted
with a base.
-‐ What do nucleophiles and bases have in common?
They both have at least one lone pair of electrons
I. Introduction to Substitution and Elimination Reactions
• When the reagent can act as a nucleophile or a base:
• Elimination and substitution will be competing
reaction pathways
Hello
• A substrate is a chemical species of particular interest
(because we are studying it).
• In the example above, which compound is the substrate?
• In this case it is the alkyl halide.
I. Introduction to Substitution and Elimination Reactions
Two main reasons why alkyl halides undergo substitution and
elimination reactions:
1. The halogen is electron-‐withdrawing, creating a partial positive
charge on the alpha carbon, making it susceptible to nucleophilic
attack. Hello
Nuc:
2. The
halogen
acts
as
a
leaving
group,
and
for
a
substrate
to
undergo
a
substitution/elimination
reaction,
it
must
possess
a
good
leaving
group.
• Good
leaving
groups
are
conjugate
bases
of
an
acid
with
a
pKa
<0.
This
is
because
the
conjugate
base
is
stabilized.
• Unstabilized
conjugate
bases
make
poor
leaving
groups,
they
are
too
high
in
energy.
I. Introduction to Substitution and Elimination Reactions
Good
leaving
groups
are
the
conjugate
bases
of
strong
acids.
Stabilized
Hello
conjugate
bases
Tosyl-OH
TsOH
Unstabilized
conjugate
bases
II. Nomenclature and Uses of Alkyl Halides
Alkyl
halides:
Compounds
where
an
sp3
carbon
group
(alkyl)
is
bonded
to
a
halide
(F,
Cl,
Br,
or
I)
• They
are
widely
synthesized
by
us
to
serve
a
variety
of
purposes
such
as…
– Hello
Insecticides
(DDT,
etc.)
– Dyes
(tyrian
purple,
etc.)
– Drugs
(anticancer,
antidepressants,
antimicrobial,
etc.)
– Food
additives
(Splenda,
etc.)
– Many
more
• The
structure
of
the
molecule
determines
its
function
• Halides
appear
in
a
wide
variety
of
natural
products.
Marine
species
and
plants
use
these
compounds
as
“chemical
warfare
agents
in
order
to
protect
themselves.
II. Nomenclature and Uses of Alkyl Halides
Cl
Cl Cl Cl Cl
Cl Cl PCB (polychlorinated biphenyls) Cl Cl
DDT (pesXcide) -‐ coolants, insulaXng fluids,
Hello N NH F F
R NO2 F
HO OH N
O
Bronopol
anX-‐microbial
agent
Cl
in baby-‐wipes Chlorpheniramine (R)-‐FluoxeXne
HO (Prozac)
OH
Cl HO
O
HO O O
Cl
OH
Cl
Sucralose or Splenda (hundreds of Xmes sweeter than sugar)
II. Nomenclature and Uses of Alkyl Halides
• Recall the steps we use to name a molecule
1. Identify and name the parent chain
2. Identify the name of the substituents
Hello
3. Assign a locant (number) to each substituents
4. Assemble the name alphabetically
• The
halide
group
is
the
key
substituent
we
will
name
and
locate.
• Halogens
are
named
the
following
way:
• fluoro-‐,
chloro-‐,
bromo-‐,
iodo-‐
prefix
is
listed
first
followed
by
the
rest
of
the
name
II. Nomenclature and Uses of Alkyl Halides
• For
each
of
these
examples,
convince
yourself
that
they
are
numbered
in
the
most
appropriate
way.
Hello
II. Nomenclature and Uses of Alkyl Halides
• Give reasonable names for the following molecules
Hello
2-‐bromo-‐2-‐iodo-‐3-‐methylbutane 2,3-‐dichloro-‐4-‐isopropyl-‐5-‐methylhexane
II. Nomenclature and Uses of Alkyl Halides
Assign
a
systematic
name
for
each
of
the
following
compounds:
F
Br Br
Br
Cl
Cl
Hello
a.
b.
c.
d.
Cl
Cl
Br Cl
Cl
e.
f.
g.
h.
II. Nomenclature and Uses of Alkyl Halides
Answers:
F
Br Br
Br
Cl
Cl
a.
Hello
b.
c.
d.
4,4-‐dibromo-‐1-‐ 1-‐bromo-‐1-‐ (R)-‐4-‐chloro-‐4-‐ 5-‐fluoro-‐2,2-‐
chloroheptane methylcyclohexane ethyloctane dimethylhexane
Cl
Cl
Br Cl
Cl
e.
f.
g.
h.
3-‐bromo-‐3-‐ (2R,3R)-‐3-‐tert-‐butyl-‐2-‐ (2R
4S)-‐2-‐chloro-‐4-‐ 2,2-‐dichloro-‐3,3-‐
isopropyl-‐2-‐ chloro-‐1,1-‐ ethyl-‐8-‐methylnonane diethyl-‐4-‐
methylnonane dimethylcyclobutane methylpentane
II. Nomenclature and Uses of Alkyl Halides
• Some simple molecules are also recognized by their
common names.
– the alkyl group is named
as the substituent, and
Hello
the halide is treated as
the parent name
Systematic Name Common Name
Cl Cl
Methylene
chloride
is
a
Cl Cl
commonly
used
organic
Dihalo alkane alkyl dihalide
solvent
Dichloromethane Methylene Chloride
(DCM)
methylene = a CH2 group
II. Nomenclature and Uses of Alkyl Halides
• Greek
letters
are
often
used
to
label
the
carbons
of
the
alkyl
group
attached
to
the
halide
– The alpha carbon is connected to
the substituent we are focused on.
Hello
– We then count away, in all directions using beta and
gamma
– There can be as many as three beta positions
II. Nomenclature and Uses of Alkyl Halides
• The
amount
of
branching
at
the
alpha
carbon
affects
the
reaction
mechanism.
There
are
three
types
of
alkyl
halides
Hello
– Primary alkyl halides only have 1 β position.
– Secondary alkyl halides have 2 β postions
– Tertiary alkyl halides have 3 β positions
II. Nomenclature and Uses of Alkyl Halides
• Some alkyl halides are used as insecticides. For the
insecticides below…
– Label each halide as either primary, secondary, or tertiary
– For the circled atoms, label all of the alpha, beta, gamma, and
delta carbons.Hello
Primary Secondary
II. Nomenclature and Uses of Alkyl Halides
• Organic halides are also useful to organic chemists as
synthetic precursors (building blocks to make more
complex molecules)
Hello Cl t-BuOK
NaOH An alkyl halide
an alkene
NaCN
OH
NaOCH3
NaSH CN
an alcohol CH3CO2Na
a nitrile
OCH3
O
an ether SH
an ester O
a thiol
III. SN2 Reactions
• A substitution reaction requires the loss of a leaving
group, and nucleophilic attack. There are two possible
mechanisms: (1) concerted, and (2) stepwise.
1. The concerted mHello
echanism involves breaking of the bond to the
leaving group and making of the bond to the nucleophile at the
same time (concerted = at the same time)
III. SN2 Reactions
2. The
stepwise
mechanism
the
leaving
groups
leaves
first,
to
give
a
carbocation
intermediate,
followed
by
nucleophilic
attack
Hello
III. SN2 Reactions
What
do
S,
N,
and
2
stand
for
in
the
SN2
name?
Hello
1 2
• How might you write a rate law for this reaction?
Rate = k [1]n[2]m
• How would you design a laboratory experiment to confirm this
rate law? Keep the concentraYon of one reactant the same,
and vary the other. Observe how the rate changes.
S = subsXtuXon, N = nucleophilic, 2 = bimolecular (second order reacXon)
III. SN2 Reactions
The following substitution reaction exhibits second-‐order
kinetics, and is therefore presumed to occur via an SN2 process.
I + NaOH OH + NaI
a. What happens to Hello
the rate if the concentration of 1-‐iodopropane
is tripled and the concentration of sodium hydroxide remains the
same?
b.
What
happens
to
the
rate
if
the
concentration
of
1-‐iodopropane
remains
the
same
and
the
concentration
of
sodium
hydoxide
is
doubled?
c.
What
happens
to
the
rate
if
the
concentration
of
1-‐iodopropane
is
doubled
and
the
concentration
of
sodium
hydroxide
is
tripled?
III. SN2 Reactions
Answers:
I + NaOH OH + NaI
a.
What
happens
to
the
rate
if
the
concentration
of
1-‐iodopropane
is
tripled
and
the
concentration
Hello of
sodium
hydroxide
remains
the
same?
3x
faster
b.
What
happens
to
the
rate
if
the
concentration
of
1-‐iodopropane
remains
the
same
and
the
concentration
of
sodium
hydoxide
is
doubled?
2x
faster
c.
What
happens
to
the
rate
if
the
concentration
of
1-‐iodopropane
is
doubled
and
the
concentration
of
sodium
hydroxide
is
tripled?
2
x
3
=
6x
faster
III. SN2 Reactions
• How
does
the
observed
stereochemistry
in
the
following
reaction
support
an
SN2
mechanism?
Hello
III. SN2 Reactions
• The
transition
state
for
the
following
reaction,
explains
why
SN2
reactions
proceed
with
inversion
of
configuration
Transition
state
symbol
(double
dagger)
Hello
H Me
HS Br
Et
Back-‐side
attack:
The
requirement
that
the
nucleophile
can
only
attack
from
the
back
side
(directly
opposite,
180°,
of
the
leaving
group)
Inversion
of
Configuration:
The
stereocenter
is
inverted
do
to
the
fact
that
the
nucleophile
attacks
from
the
back-‐side.
(see
transition
state
above)
III. SN2 Reactions
When
(R)-‐2-‐bromobutane
is
treated
with
sodium
hydroxide,
a
mixture
of
products
is
obtained.
An
SN2
process
is
responsible
for
generating
one
of
the
minor
products,
while
the
major
product
is
generated
via
an
elimination
process,
as
will
be
discussed
later
in
this
chapter.
Draw
the
SN2
product
that
is
obtained
when
(R)-‐2-‐
Hello
bromobutane
reacts
with
a
hydroxide
ion.
III. SN2 Reactions
When
(R)-‐2-‐bromobutane
is
treated
with
sodium
hydroxide,
a
mixture
of
products
is
obtained.
An
SN2
process
is
responsible
for
generating
one
of
the
minor
products,
while
the
major
product
is
generated
via
an
elimination
process,
as
will
be
discussed
later
in
this
chapter.
Draw
the
SN2
product
that
is
obtained
when
(R)-‐2-‐
Hello
bromobutane
reacts
with
a
hydroxide
ion.
Br
1 + NaOH ?
3 2
OH
(R)-‐2-‐bromobutane
Make it easy for yourself and
always have the H in the back! (S)-‐2-‐butanol
Inversion of Stereochemistry
due to the back-‐side attack
III. SN2 Reactions
Draw the product for each of the following SN2 reactions.
a. (S)-‐2-‐Chloropentane and NaSH
Hello
b. (R)-‐3-‐Iodohexane and sodium chloride
c. (R)-‐2-‐Bromohexane and sodium cyanide
d. 1-‐Bromoheptane and sodium hydroxide
III. SN2 Reactions
Answers:
Cl SH
a. + NaSH
Hello
b.
+ NaCl
I Cl
Br CN
c.
+ NaCN
Br OH
d.
+ NaOH
III. SN2 Reactions
A
common
method
for
confirming
the
proposed
structure
and
stereochemistry
of
a
natural
product
is
to
synthesize
the
proposed
structure
and
then
compare
its
properties
with
those
of
the
natural
product.
Draw
curved
arrows
for
both
steps
shown
below
Hello
Br Br
H
O KO O O
H
H H
H
1 2 3
III. SN2 Reactions
Answers:
Br Br
Hello H
O KO O O
H
H H
H
1 2 3
III. SN2 Reactions
Mechanism
of
an
SN2
Reaction
(MO
Theory)
• The
nucleophile
attacks
from
the
back-‐side
– Electron
density
repels
the
attacking
nucleophile
from
the
front-‐side
(presence
of
bonded
pair
of
electrons)
– The
nucleophile
must
approach
the
back-‐side
to
allow
Hello
electrons
to
flow
from
the
HOMO
of
the
nucleophile
to
the
LUMO
of
the
electrophile.
(LUMO
is
the
anti-‐bonding
orbital)
– Proper
orbital
overlap
cannot
occur
with
front-‐side
attack
because
there
is
a
node
on
the
front-‐side
of
the
LUMO
we compare the relative rates presented in Table 7.2, the following trends emerg
III. SN2 Reactions
e of an SN2 reaction is most sensitive to the number of substituents at the α p
bromide
Rates
oisf
pover onevhundred
rimary
timesvs
more
s
secondary
reactive
tertiary
alkyl
than ethyl bromide (a prima
halides
which is over one hundred times more reactive than isopropyl bromide (a se
• Less
lide). Noticesterically
that t-butyl hindered
bromidee(a lectrophiles
tertiary alkylreact
halide)mis
ore
readily
towa
unreactive
bservations
under
indicate
SN2
cthat SN2 reactions
onditions.
are most
Tertiary
effective
halides
fortoo
are
methyl halides and
hindered
lides, and SN2 reactions cannot be performed with tertiary alkyl halides.
to
react
via
SN2
Hello
mechanism.
Reactivity toward SN2
Most
Unreactive
reactive
H3C X
X X X
Methyl 1° 2° 3°
• To
7.2
TABLE
rationalize
this
trend,
examine
the
EFFECT OF SUBSTITUENTS ON THE RATES OF SN2 REACTIONS
reaction
coordinate
diagram.
⊝
⊝
R Br R + Br
acetone
III. SN2 Reactions
• Alkyl
groups
branching
from
the
α
and
β
carbons
hinder
the
backside
attack
of
the
nucleophile,
resulting
in
a
slower
rate
of
reaction.
Hello
III. SN2 Reactions
To
rationalize
this
trend,
we
must
examine
the
energy
diagram
• What
feature
of
the
diagram
is
relevant
to
rationalize
the
rate
of
reaction?
• What
feature
is
relevant
to
rationalize
the
thermodynamics
of
the
reaction? Hello
III. SN2 Reactions
• Which
reaction
will
have
the
fastest
rate
of
reaction?
• WHY?
H H 3C H 3C
X X X
Nuc: H Nuc: H Nuc: H
H H H 3C
Hello
• 3° substrates react too slowly to measure. Other reactions
are possible, and will happen more quickly.
III. SN2 Reactions
As a class, lets draw the transition state of the following
reaction:
NaSH
Cl SH + NaCl
Hello
III. SN2 Reactions
Answer:
Back-‐side
attack!
As
the
HS−
come
in,
the
Cl−
leaves.
NaSH
Cl SH + NaCl
Hello
CH3
SH Cl
H H
III. SN2 Reactions
Draw
the
transition
state
for
each
of
the
following
SN2
reactions:
Br NaOH OH
a.
+ NaBr
O
Hello
b.
O
O
I +
I
O
c.
Cl
NaOH
OH + NaCl
Br SH
d. NaSH
+ NaBr
III. SN2 Reactions
a.
c.
Hello HO Cl
HO Br
H H
H H
Br
b.
O
I
d.
H
O H H SH
III. SN2 Reactions
The
total
synthesis
of
the
marine
natural
product
aldingenin
C
in
the
laboratory
utilized
an
intramolecular
SN2-‐type
reaction
which
utilized
a
poor
leaving
group.
However,
in
this
case
the
reaction
was
favorable
do
the
the
relief
of
ring
strain
(opening
of
a
3-‐
membered
ring).
The
relief
of
ring
strain
can
be
a
powerful
driving
force
in
reactions!
DHello
raw
the
transition
state
for
this
reaction
and
identify
the
leaving
group.
O O
O
O
O
O
III. SN2 Reactions
Answer:
Drawing
these
structures
in
3D
often
works
best!
Hello O
O
IV. Nucleophilic Strength and Solvent Effects in SN2
Reactions
• What
are
the
factors
that
contribute
to
the
strength
of
a
nucleophile? Polarizability and Charge
• A
strong
nucleophile
Hello i s
n eeded
for
a n
S N2
rxn
• We need to be able to recognize a given nucleophile as
being strong or weak
IV. Nucleophilic Strength and Solvent Effects in SN2
Reactions
Commonly nucleophiles used in substitution reactions:
Hello
• You
should
be
able
to
determine
if
a
nucleophile
is
strong
or
weak.
• In
general,
anions
are
strong
nucleophiles
• If
there
is
no
charge,
it
tends
to
be
a
weaker
nucleophile
• Polarizable
atoms
are
good
nucleophiles
• Polarizable
=
ability
to
unevenly
distribute
its
electron
density
do
to
an
external
influence.
(More
electrons
are
pulled
toward
the
electrophile)
• Large
atoms
like
S,
Cl,
Br,
and
I
• The
solvent
affects
nucleophilicity
IV. Nucleophilic Strength and Solvent Effects in SN2
Reactions
• Need a polar aprotic solvent for SN2 rxns
Hello
• Protic solvents engage in H-‐bonding, and stabilize anionic species
(such as good nucleophiles).
• Hydrogen bonds are very very good at this!
• Aprotic
solvents
stabilize
both
cations
and
anions
(but
they
do
not
stabilize
anions
as
well
due
to
steric
constraints)
IV. Nucleophilic Strength and Solvent Effects in SN2
Reactions
• How
do
these
factors
play
into
the
strength
of
a
nucleophile
in
protic
versus
aprotic
solvent?
• Nucleophiles are less stable,
thus more reactive Hello
in aprotic
solvent.
• The activation energy will be
lower and the reaction faster
Aprotic solvents are
best for SN2 reactions
IV. Nucleophilic Strength and Solvent Effects in SN2
Reactions
Hello
Nucleophiles are more reactive in aprotic solvents
IV. Nucleophilic Strength and Solvent Effects in SN2
Reactions
For each pair of reactions, which one will exhibit a faster rate?
Explain.
Cl NaOH/H2O OH
a.
i.
+ Cl
Hello
NaOH/DMSO
ii.
Cl OH + Cl
b.
i.
Br NaI / EtOH I +
Br
ii. Br NaCl / EtOH Cl +
Br
IV. Nucleophilic Strength and Solvent Effects in SN2
Reactions
Answers:
Cl NaOH/H2O OH
a.
i.
+ Cl
NaOH/DMSO
ii.
Cl
Hello OH + Cl
ii.
is
fastest
since
the
DMSO
(an
operatic
solvnet)
does
NOT
stabilize
the
nucleophile
as
well
as
H2O
does
(a
protic
solvent).
b.
i.
Br NaI / EtOH I +
Br
ii. Br NaCl / EtOH Cl +
Br
i.
is
fastest
since
I−
is
a
more
polarizable
and
therefore
a
better
nucleophile!
Cl−
is
not
as
polarizable
so
it
will
not
react
as
quickly
therefore
ii.
reacts
more
slowly.
V. SN2 Reactions in Biological Systems—Methylation
Alkylation: The transfer of an alkyl group to a nucleophile
Methylation: The transfer of a methyl group to a nucleophile.
H3C
Hello
I
Nuc Nuc CH3 + I
SN2
• In
lab,
methyl
iodide
is
regularly
used.
It
is
a
liquid
at
room
temperature
which
is
easy
to
handle
and
I−
is
an
excellent
leaving
group
due
to
its
polarizability
and
ability
to
stabilize
a
negative
charge.
V. SN2 Reactions in Biological Systems—Methylation
• Halides
are
common
leaving
groups
for
laboratory
use,
but
are
not
common
substrates
in
biological
SN2
rxns.
Good
Good
Hello leaving
leaving
group
group
Laboratory
methylaYng
agent Biological
methylaYng
agent
• Both
of
these
compounds
are
good
methylating
reagents:
a
good
nucleophile
will
attack
the
CH3
via
an
SN2
mechanism.
V. SN2 Reactions in Biological Systems—Methylation
O
triphosphate
O P O
O
very
complex
leaving
group O leaving
group O
H 3N
O P O O O P O
NH2
O NH2 O
N
O P O N N + O P O
O N
O S
O SN2 Me N O
N
H 3N
O
N
Hello
N O O P O
O
S OH OH
OH OH
S-Adenosylmethionine (SAM)
Me Adenosine triphosphate (ATP) OH
Methionine
HO NH2
Sulfur is a great -H+
nucleophile HO
Noradrenaline
OH
H
HO N
Me
HO
Adrenaline
VI. Introduction to E2 Reactions
• When
an
alkyl
halide
is
treated
with
a
strong
base,
it
can
undergo
beta
elimination
(1,2-‐elimination)
to
form
an
alkene:
Hello
• A
strong
base
will
react
in
a
concerted
mechanism,
called
an
E2
elimination.
VI. Introduction to E2 Reactions
• E2 elimination is concerted. The base removes a β-‐proton, causing
the loss of the leaving group and the formation of the C=C bond.
So, concerted elimination is bimolecular and follows second-‐order
kinetics:
Hello
• In
what
ways
is
E2
elimination
similar
to
SN2
substitution?
What
are
the
differences?
Similar: SXll second order
Akack happens 180° from the leaving group
Concerted (all happens at once)
Leaving group sXll leaves
VI. Introduction to E2 Reactions
• E2 elimination is concerted. The base removes a β-‐proton, causing
the loss of the leaving group and the formation of the C=C bond.
So, concerted elimination is bimolecular and follows second-‐order
kinetics:
Hello
• In
what
ways
is
E2
elimination
similar
to
SN2
substitution?
What
are
the
differences?
Different: An alkene is formed
Akack happens at the β posiXon to abstract a hydrogen
Base is required; has to be strong enough to yank off a hydrogen
VI. Introduction to E2 Reactions
Which reaction will occur??
• Consider a reagent such as NaOH, which is a strong nucleophile
(good for SN2 reactions) and a strong base (good for E2 rxns)…
Hello
…
when
the
substrate
is
sterically
hindered,
E2
elimination
will
occur.
VI. Introduction to E2 Reactions
The
following
reaction
exhibits
a
second-‐order
rate
equation:
Cl NaOH
a. What happens to the rate if the concentration of
chlorocyclopentane Hello is tripled and the concentration of sodium
hydroxide remains the same?
b. What happens to the rate if the concentration of
chlorocyclopentane remains the same and the concentration of
sodium hydoxide is doubled?
c. What happens to the rate if the concentration of
chlorocyclopentane is doubled and the concentration of sodium
hydroxide is tripled?
VI. Introduction to E2 Reactions
Answers:
Cl NaOH
a. What happens to the rate if the concentration of
chlorocyclopentane Hello is tripled and the concentration of sodium
hydroxide remains the same?
3x faster
b. What happens to the rate if the concentration of
chlorocyclopentane remains the same and the concentration of
sodium hydoxide is doubled?
2x faster
c. What happens to the rate if the concentration of
chlorocyclopentane is doubled and the concentration of sodium
hydroxide is tripled? 2 x 3 = 6x faster
VII. Nomenclature and Stability of Alkenes
Learning to Name Alkenes!
• Alkenes are given IUPAC names using the same
procedure to name alkanes, with minor modifications
1. Identify the parent chain, which includes the C=C double bond
Hello
2. Identify and Name the substituents
3. Assign a locant (and prefix if necessary) to each substituent.
Give the C=C double bond the lowest number possible
4. List the numbered substituents before the parent name in
alphabetical order. Ignore prefixes (except iso) when ordering
alphabetically
5. The C=C double bond locant is placed either just before the
parent name or just before the -‐ene suffix
1. -‐ane was used for alkanes, -‐ene is used for alkenes
VII. Nomenclature and Stability of Alkenes
1. Identify
the
parent
chain,
which
should
include
the
C=C
double
bond
• The
name
of
the
parent
chain
should
end
in
-‐ene
rather
than
–ane
Hello
• The parent chain should include the C=C double bond
• If
the
double
bond
is
on
the
first
carbon,
we
don't
need
to
specify
it.
VII. Nomenclature and Stability of Alkenes
2. Identify and Name the substituents
3. Assign a locant (and prefix if necessary) to each substituent. Give
the C=C double bond the lowest number possible
Hello
– The
locant
of
the
double
bond
is
a
single
number,
and
is
the
number
indicating
where
the
double
bond
starts.
The
alkene
above
is
located
at
the
“2”
carbon.
VII. Nomenclature and Stability of Alkenes
4. List the numbered substituents before the parent name in
alphabetical order. Ignore prefixes (except iso) when ordering
alphabetically
5. The C=C double bond locant is placed either just before the
parent name or jHello
ust before the -‐ene suffix
Note:
This
alkene
has
the
E
configuration,
which
must
be
indicated
in
the
name,
in
parentheses:
(E)-‐5,5,6-‐trimethylhept-‐2-‐ene
VII. Nomenclature and Stability of Alkenes
Recall how to assign E or Z to alkene stereoisomers…
• First,
prioritize
the
groups
attached
to
the
C=C
double
bond
based
on
atomic
number
Hello
VII. Nomenclature and Stability of Alkenes
• If
the
top
priority
groups
are
cis
to
each
other,
it
is
the
Z
isomer
• If the top priority
Hello groups a re t rans to each o ther, i t i s the
E isomer
VII. Nomenclature and Stability of Alkenes
Provide a systematic name for each of the following compounds:
a.
b.
c.
Hello
d. e. f.
g.
h.
VII. Nomenclature and Stability of Alkenes
Answers:
instead
of
-‐ane
use
-‐ene
and
make
sure
the
double
bond
gets
the
lowest
number
possible.
It
is
the
highest
priority
group.
Finally,
don't
forget
E
and
Z
to
show
the
geometry
of
the
double
bond.
7
2 4 6 1 2 5 6
1 3 5
1
a.
b.
3
4
c. 2
3
4
5
(E)-‐3-‐methyl-‐3-‐hexene (E)-‐3-‐ethyl-‐4-‐methyl-‐2-‐pentene
Hello 2,3,5-‐trimethyl-‐2-‐heptene
1
4 5 2
1
d.
2
3
6
7
e.
3
5
f.
4 6 2
7 5 4 3 1
3-‐ethyl-‐2-‐methyl-‐2-‐heptene 4-‐tert-‐butyl-‐1-‐heptene
3-‐isopropyl-‐2,4-‐dimethylpentene
1 2 3
4 5 1 2
3 4
g.
6
7
h. 5 6
8
(E)-‐4,5-‐diethyl-‐2,2,7-‐trimethyl-‐4-‐octene (E)-‐3-‐ethyl-‐2,2,4,5,5-‐pentamethyl-‐3-‐hexene
VII. Nomenclature and Stability of Alkenes
Classify
each
of
the
following
alkenes
as
monosubstituted,
disubstituted,
trisubstituted
or
tetrasubstituted
a.
b.
c.
Hello
d.
e.
VII. Nomenclature and Stability of Alkenes
Answers:
a.
b.
c.
Hello
trisubsYtuted disubsYtuted trisubsYtuted
d.
e.
trisubsYtuted monosubsYtuted
VII. Nomenclature and Stability of Alkenes
Common
Names
for
some
Alkenes!
Hello
Ethylene
Propylene
Styrene
IUPAC Recognized substituents (like we did with isopropyl)
Methylene Vinyl Allyl
VII. Nomenclature and Stability of Alkenes
Which alkene is more stable?
Hello
cis-‐2-‐butene trans-‐2-‐butene
VII. Nomenclature and Stability of Alkenes
• Because
of
steric
strain,
cis
isomers
are
generally
less
stable
than
trans
Hello
VII. Nomenclature and Stability of Alkenes
• The difference in stability can be quantified by
comparing the heats of combustion
Hello
• Think
about
how
the
heats
of
combustion
of
the
cis
and
trans
isomers
reveal
their
relative
stability…
VII. Nomenclature and Stability of Alkenes
Hello
VII. Nomenclature and Stability of Alkenes
• Alkyl groups stabilize the C=C pi bond via hyperconjugation.
Hello
More alkyl groups = more stable alkene
VII. Nomenclature and Stability of Alkenes
Arrange each set of isomeric alkenes in order of stability
a.
Hello
b.
c.
VII. Nomenclature and Stability of Alkenes
Answers:
Most
stable
=
tetrasubstituted,
then
tri,
then
di.
least
stable
=
mono
substituted,
look
out
for
ring
strain!
No ring strain with 5-‐
a. membered rings or larger
Hello
most stable least stable intermediate stability
(tetrasubsYtuted) (disubsYtuted) (trisubsYtuted)
b.
intermediate
stability
most
stable
least
stable
(disubsYtuted) (trisubsYtuted) (monosubsYtuted)
c.
most
stable
even
though
least
stable
even
though
it
is
monosubsXtuted
it
is
disubsXtuted
(no
ring
strain) (severe
ring
strain)
VII. Nomenclature and Stability of Alkenes
• In
cyclic
alkenes
with
less
than
7
carbons
in
the
ring,
only
cis
alkenes
are
stable.
WHY?
Too
much
ring
strain!
Hello
• So
we
do
not
need
to
indicate
if
the
alkene
is
cis
or
trans
unless
the
ring
contains
8
carbons
or
more.
• When applied to bridged bicycloakenes, this rule is called
Bredt’s rule
VII. Nomenclature and Stability of Alkenes
• Apply Bredt’s rule to the compounds below
Hello
• The
bridgehead
carbon
cannot
have
a
trans
pi
bond
unless
one
of
the
rings
has
at
least
8
carbons
(otherwise
the
geometry
of
the
bridgehead
prevents
parallel
overlap
of
the
p-‐orbitals)
• Try
building
a
handheld
model
of
each
compound
shown
above,
and
see,
first-‐hand,
the
relative
geometric
strain
of
each
• Don’t
take
my
word
for
it,
you
have
to
see
it!
VIII. Regiochemical and Stereochemical Outcomes for E2
Reactions
Alkenes:
Thermodynamic
vs
the
Kinetic
Product
• It
is
common
for
a
substrate
to
have
more
than
one
β-‐carbon
that
can
be
deprotonated
by
a
strong
base,
and
so
E2
elimination
results
in
more
than
one
alkene
product.
Hello
Zaitsev product Hofmann product
• When ethoxide is used as the strong base, 2-‐methyl-‐2-‐
bromobutane gives two E2 products (shown above), with the more
stable alkene (the Zaitsev product) produced as the major product,
and the less substituted alkene (the Hofmann product) is the minor
product.
VIII. Regiochemical and Stereochemical Outcomes for E2
Reactions
• E2 elimination is a regioselective:
Hello
Zaitsev
product
• When constitutional isomers are formed as the products of a
reaction, with one of them as the major product, the reaction is
regioselective
• The
regioselectivity
of
an
E2
reaction
can
be
controlled
by
carefully
choosing
the
strong
base
used.
VIII. Regiochemical and Stereochemical Outcomes for E2
Reactions
• Experimental
data
indicates
that
a
bulky,
sterically
hindered
base
will
favor
the
formation
of
the
Hofmann
product,
but
an
unhindered
base
(like
ethoxide)
will
favor
the
Zaitsev
product:
Hello
Provide a rational for the observed results.
VIII. Regiochemical and Stereochemical Outcomes for E2
Reactions
• Why does a sterically hindered base favor the Hofmann product?
Since the base is so big, the other hydrogen is too sterically hindered
• Sterically hindered bases (also called non-‐nucleophilic bases) are
useful in many reactions
Hello
VIII. Regiochemical and Stereochemical Outcomes for E2
Reactions
Predict the major and minor products of the following E2
reaction.
NaOMe
Hello
Cl
Answers:
First
determine
where
the
beta
hydrogens
are.
Second,
a
small
base
will
react
with
the
most
thermodynamically
stable
intermediate
which
will
give
the
most
thermodynamically
stable
product.
A
bulky
base
will
react
with
H H
H H
whatever
hydrogen
is
the
most
accessible
H H
(easiest to grab) and often gives the least H H
H
thermodynamically Hello stable product. H Cl
H
These hydrogens are idenYcal!
These are more hindered but “locked into This methyl group is freely spinning
conformaYon” due to the thermodynamic due to a low energy barrier of rotation.
Its more likely to not be in the proper
stability of the equatorial methyl group conformation for elimination, but it is
easily accessible to a large base
β
β
NaOMe
Cl
β Major
product
Minor
product
(a
small
base
was
used) (Would
be
favored
if
a
large
base
was
used)
VIII. Regiochemical and Stereochemical Outcomes for E2
Reactions
Predict
the
major
and
minor
products
for
each
of
the
following
E2
reactions.
Cl
a. NaOEt
Hello
Cl
b. t-BuOK
I
NaOEt
c.
VIII. Regiochemical and Stereochemical Outcomes for E2
Reactions
Answers:
Smaller
bases
allow
for
the
most
thermodynamically
stable
product.
Larger
bases
grab
onto
the
most
accessible
hydrogen
making
the
kinetic
(often
less
stable
product)
Cl
a.
NaOEt +
Hello
major minor
Cl
b.
t-BuOK
+
minor major
I
NaOEt
c. +
major minor
VIII. Regiochemical and Stereochemical Outcomes for E2
Reactions
Predict
the
major
and
minor
products
for
each
of
the
following
E2
reactions.
d.
I
t-BuOK
Hello
Br
NaOEt
e.
Br
t-BuOK
f.
VIII. Regiochemical and Stereochemical Outcomes for E2
Reactions
Answers:
Smaller
bases
allow
for
the
most
thermodynamically
stable
product.
Larger
bases
grab
onto
the
most
accessible
hydrogen
making
the
kinetic
(often
less
stable
product)
I
d.
t-BuOK
+
Hello minor major
Br
NaOEt
e.
only product
Br
t-BuOK
f.
only product
VIII. Regiochemical and Stereochemical Outcomes for E2
Reactions
For
each
of
the
following
reactions,
identify
whether
you
would
use
ethoxide
or
t-‐butoxide
to
accomplish
the
desired
transformation.
Hello
a.
Cl
b.
Br
VIII. Regiochemical and Stereochemical Outcomes for E2
Reactions
Answers:
Smaller
bases
allow
for
the
most
thermodynamically
stable
product.
Larger
bases
grab
onto
the
most
accessible
hydrogen
making
the
kinetic
(often
less
stable
product)
HelloNaOEt
a.
Cl
t-‐BuOK
b.
Br
VIII. Regiochemical and Stereochemical Outcomes for E2
Reactions
• Consider
the
dehydrohalogenation(removal
of
XH)
of
3-‐
bromopentane,
where
two
stereoisomers
are
possible
products:
Hello
Draw a Newman projection for each of these, rationalize
why one is preferred over the other!
VIII. Regiochemical and Stereochemical Outcomes for E2
Reactions
• Consider the dehydrohalogenation(removal of XH) of 3-‐
bromopentane, where two stereoisomers are possible products:
Hello
Use this energy diagram and
the Hammond postulate to
explain why the trans isomer is
formed stereoselectively
Trans is the thermodynamic & kinetic product
mple,
VIII.theRegiochemical
β position had two different protons:
and Stereochemical Outcomes for E2
Reactions Br
In such a case, both the cis and the trans isomers were produced, w
theNow
cis andlet’s
the trans isomers
consider a were
case produced,
where the with
β the trans isomer
position being only
contains favored.
one
• Consider dehydrohalogenation of the alkyl halide below:
case where the β position contains only one proton. For example, consider per-
forming an elimination reaction with the following substrate:
ion reaction with the following substrate:
There is Br
Ph only one β Ph Br
Me hydrogen
βthat can be Me α β
α
Ph = Ph =
removed
β
Hello β
H H H H
re are two β positions. One of these positions has no protons at all, and the other
• In this
You
example,
m ight
i there
magine
t are
hat
i two
t
w β positions.
ould
b e
e proton. In such a case, a mixture of stereoisomers is not obtained. In thisp One
ossible
to
f of these
orm
b oth
tpositions
he
case,
E
and
Z
ahas
position
ne stereoisomeric lkene
products,
only
product: one proton. but
only
Inthe
such E
isomer
a case,is
aformed
mixture of stereois
there will
Ph only
Br be one stereoisomeric
Ph H product: Ph
Me NaOEt
Ph Br Ph
H H MeMe Me
NaOEt H
this
isomer
is
only
product Me
ssible stereoisomer not obtained? To understand H H answer to
the not
formed
this question, we
gnment of Why
orbitalsis
inthere
only
one
the transition state. product
formed
state,
In the transition in
this
a π bondcase?is form-
bondWhyis comprised
is the other of overlapping
possiblep stereoisomer
orbitals. Therefore, notthe transition To
obtained? stateundersta
must
VIII. Regiochemical and Stereochemical Outcomes for E2
Reactions
• To
rationalize
the
stereospecificity
of
the
reaction,
consider
the
transition
state
for
the
reaction
• In
the
transition
state,
the
C-‐H
and
C-‐Br
bonds
that
are
breaking
must
be
rotated
into
the
same
plane
as
the
pi
bond
that
is
forming
Hello
• In
other
words,
the
β-‐hydrogen
and
the
leaving
group
must
be
co-‐
planar.
VIII. Regiochemical and Stereochemical Outcomes for E2
Reactions
leophilic Substitution and
ides: Nucleophilic Elimination
Substitution and Reactions
Elimination Reactions
• There
are
two
rotamers
where
the
β-‐hydrogen
and
the
leaving
atRecall that thesingle
the C−C C−C single
bond is bond
free toisrotate
free tobefore
rotate before the reaction
the reaction occurs.
occurs. If we Ifimagine
we imagin
rot
d,this
group
we bond,
see that
asee
wetherere
that
care
oplanar:
there are two
two ways to ways to achieve
achieve a coplanar
a coplanar arrangement:
arrangement:
Ph Ph Br HBr Br
Br H
Me Me Rotate theRotate the C C bond
C C bond
Ph Ph
H Hello
H Me H
H H Me H
The first conformation is called anti-coplanar, while the second conformation is called syn-
conformation is called anti-coplanar, while the second conformation is called syn-copl
In this context, the terms anti and syn refer to the relative positions of the proton and th
ontext, the terms
• Since
e
aanti cand syn refertwo
to the relative positions ofthe
theNproton and the le
group, whichw can re
seen
be omparing
more clearly with different
Newmanrotamers,
projections: ewman
hich can be seen more
projections
clearly
are
with
a
good
Newman
tool
projections:
to
compare
them
Br H Br
Br Me Ph H Br
Me Ph t-Bu
t-Bu H Ph Me
t-Bu H
t-Bu H H Ph Me
H
H Anti-coplanar Syn-coplanar
(staggered)
Anti-coplanar (eclipsed)
Syn-coplanar
(staggered) (eclipsed)
When viewed in this way, we can see that the anti-coplanar conformation is staggered, whi
ewed in this
coplanar way, we canis see
conformation that the
eclipsed. anti-coplanar
Elimination conformation
via the syn-coplanarisconformation
staggered, while
wouldth
context, the terms antiMe
and syn refer to the relative
Rotate the positions
C C bond of the proton and the
VIII. Regiochemical and
which can be seen more clearly with
Stereochemical
Newman projections:
Outcomes
Ph for E2
H H Me H
Reactions
The first conformation is calledBranti-coplanar, whileH Br the second conformation is cal
The
staggered
rotamer,
where
the
βto-‐hydrogen
In• this context, the terms anti and syn refer t-Bu
Me Ph and
leaving
group
the relative positions of the proto
group,are
anti-‐coplanar
(more
or
anti-‐periplanar),
Ph is
is
tprojections:
he
Me only
conformation
which can be seent-Bu H
clearly with Newman H
where
elimination
can
H occur.
(electrons
can
properly
flow
into
the
Anti-coplanar Syn-coplanar
anti
bonding
orbitals)
(staggered) Br (eclipsed) H Br
Me Ph
viewed in this way, we can Hello see that the
t-Bu
anti-coplanar
H
conformation
t-Bu isMestaggered, while
Ph
ar conformation is eclipsed. Elimination Hvia the syn-coplanar conformation H would in
on state of higher energy as a result of Anti-coplanar
the eclipsed geometry.Syn-coplanar
Therefore, elimination occu
(staggered) (eclipsed)
via the anti-coplanar conformation. In fact, in most cases, elimination is observed t
• via The
vely
When the
viewed product
in thisresulting
anti-coplanar from
conformation,
way, we can seetthat
he
which athe
nti-‐periplanar
leads rotamer
to one specific
anti-coplanar is
formed
stereoisomeric
conformation prod
is stagge
coplanar conformationBr
is eclipsed. Elimination via the syn-coplanar conformation
Me Ph
transition stateMe of higher
Ph energy as
Elimination
a result Me
of the eclipsed
Ph
geometry. Therefore, elimin
rapidly viat-Bu the anti-coplanar
H
conformation.
t-Bu In fact,H in most cases, elimination is
exclusively via the H anti-coplanar conformation, which leads to one specific stereoiso
t-Bu H
Anti-coplanar
(staggered) Br Me Ph
Me Ph Me
Elimination Ph
e requirement for coplanarity is not entirely absolute.
t-Bu That is, small
H deviations from co
VIII. Regiochemical and Stereochemical Outcomes for E2
Reactions
• Evidence
suggests
that
a
strict
180°
angle
is
not
necessary
for
E2
mechanisms.
• Similar
angles
(175–179°)
are
sufficient
• The
term,
anti-‐periplanar
Hello is
generally
used
instead
of
anti-‐coplanar
to
account
for
slight
deviations
from
coplanarity
• Although
the
E
isomer
is
usually
more
stable
because
it
is
less
sterically
hindered,
the
requirement
for
an
anti-‐
periplanar
transition
state
can
often
lead
to
the
less
stable
Z
isomer
VIII. Regiochemical and Stereochemical Outcomes for E2
Reactions
Identify
the
major
and
minor
products
for
the
E2
reaction
that
occurs
when
each
of
the
following
substrates
is
treated
with
a
strong
base
Hello
a.
Cl
b.
Cl
VIII. Regiochemical and Stereochemical Outcomes for E2
Reactions
more
stable,
t-‐ less
stable,
t-‐butyl
Answer:
In
both
cases,
butyl
and
n-‐butyl
and
n-‐butyl
groups
groups
are
anti
regiochemistry
is
irrelevant
are
Gauche
Cl Cl
because
there
is
only
one
β
H H
position that bears protons. H
H
H
H
Hello
a.
+
Cl
major
product minor
product
Stereoselective,
there
are
2
protons
to
choose
from
b. Cl
Cl
Stereospecific,
there
is
only
one
β
proton
available,
so
Make
sure
you
either
draw
your
H
H only
one
product
can
form
Newman
Projections
or
rotate
the
C-‐C
bonds
until
the
Cl
and
the
H
are
anti.
VIII. Regiochemical and Stereochemical Outcomes for E2
Reactions
Identify
the
major
and
minor
products
for
the
E2
reaction
that
occurs
when
each
of
the
following
substrates
is
treated
with
a
strong
base
Cl Cl
Br
a.
d.
g.
Hello
Cl Cl
b.
e.
h.
Br
Cl
Br
c.
f.
VIII. Regiochemical and Stereochemical Outcomes for E2
Reactions
Answers:
Draw
all
transition
states
where
the
H
and
the
halogen
are
anti.
Determine
which
is
most
stable
(less
steric
Gauche
interactions),
then
draw
the
product.
Drawing
Newman
projections
is
very
helpful
here!
Br C 6H 5
H Br
Ha Hb
Hello Ha Hb
Hb
a. major product
C 6H 5
Br t-Bu
Br Ha Hb
H
Ha Hb
Ha
minor
product
C 6H 5
b. Br H Br
Br
C 6H 5
t-Bu
t-Bu
rotate C-Cbond C 6H 5
H 3C H
H 3C H
H
only
product
VIII. Regiochemical and Stereochemical Outcomes for E2
Reactions
Answers:
Draw
all
transition
states
where
the
H
and
the
halogen
are
anti.
Determine
which
is
most
stable
(less
steric
Gauche
interactions),
then
draw
the
product.
Drawing
Newman
projections
is
very
helpful
here!
C 6H 5
Br H Br
c.
H CH3
Hello
Cl
H Cl
d.
H
C 6H 5
Cl
Cl H
e. Me H
C 6H 5
VIII. Regiochemical and Stereochemical Outcomes for E2
Reactions
Answers:
Draw
all
transition
states
where
the
H
and
the
halogen
are
anti.
Determine
which
is
most
stable
(less
steric
Gauche
interactions),
then
draw
the
product.
Drawing
Newman
projections
is
very
helpful
here!
Cl CH3
f. H Cl rotate C-Cbond Cl C 6H 5 H
Hello
H C
C H
H3
6 5
H 3C
H
H
C 6H 5
Cl
H Cl
H
g. Hb Ha Ha Hb
C 6H 5
Hb
major
product
rotate C-Cbond
Cl C 6H 5
Ha Hb minor
product
H Ha
H
VIII. Regiochemical and Stereochemical Outcomes for E2
Reactions
Answers:
Draw
all
transition
states
where
the
H
and
the
halogen
are
anti.
Determine
which
is
most
stable
(less
steric
Gauche
interactions),
then
draw
the
product.
Drawing
Newman
projections
is
very
helpful
here!
h. Cl
Hello Cl H Ha
Ha Hb
C 6H 5
rotate C-Cbond major product
Hb
C 6H 5 Cl
Ha Hb
H
minor
product
VIII. Regiochemical and Stereochemical Outcomes for E2
Reactions
• For the following substrate, the β-‐carbon has TWO β-‐hydrogens
• There are two different rotamers where a β-‐hydrogen is anti-‐
periplanar to the leaving group, and so two stereoisomers will be
formed.
Hello
• In this case, the reaction will be stereoselective, but not
stereospecific. (depends on the stereochemistry of the transition
state, but multiple products are possible)
• E2 elimination will be stereospecific only when both the α and β
carbons are stereocenters (only one product can be formed)
Br
VIII. Regiochemical and Stereochemical Outcomes for E2
e cis andReactions
the trans isomers were produced, with the trans isomer being favored.
se where the β position contains only one proton. For example, consider per-
nStereoselective: A single ssubstrate:
reaction with the following ubstrate can product two potential products.
Ph Br
Me α β Ph =
β
H H
areStereospecific:
two β positions.OOne ne
sof these positions
Hello
tereoisomer
can
has no fprotons
only
at pall,
orm
one
and the
If
other
roduct.
you
flip
proton. In such ya ou
the
chirality,
case, a mixture
will
of stereoisomers
get
a
different
is not
product.
obtained. In this case,
stereoisomeric product:
Ph Br Ph H Ph
Me NaOEt
H H Me Me H
this
isomer
is
only
product
ble stereoisomer not obtained? To understand the answer to thisnot
formed we
question,
ment of orbitals inMethe transition
Br state. In the transition state,
Ph a π bond
t-Bu is form-
nd is comprisedPhof overlapping p orbitals.NaOEtTherefore, the transition state must
of p orbitals that are
H positioned
H
t-Bu such that they can overlap Me with each
H other as
rder to achieve this kind of orbital overlap, the following four atoms must all
VIII. Regiochemical and Stereochemical Outcomes for E2
Reactions
• It is very important to understand the difference between the
terms stereospecific and stereoselective.
Hello
• In a stereospecific reaction, the substrate is stereoisomeric and
results in one stereoisomer as the product
• In a stereoselective reaction, the substrate can produce two
stereoisomers as products, where one is the major product.
CH3 H3C H CH3 H3C CH3 H3C H CH3
VIII. Regiochemical
9 5 3 and Stereochemical Outcomes
9 5 for3 E2
6 2 6 2
Reactions
8
7
4
O
8
7
4
Br 1 Br 1
CH3 O CH3 CH3 O
• Consider the dehydrohalogenation of a cyclohexane derivative,
Base Base
where the leaving group is attached to the ring
Compound 1 Compound 2
roblems 7.61, 7.62, 7.74
Hello
specificity of E2 Reactions on Substituted Cyclohexanes
vious section, we explored the requirement that an E2 reaction proceed via an a
• Given the a nti-‐periplanar requirement, E
mation. That requirement has special significance when dealing with substitute2 elimination can o nly
ll that occur when tcyclohexane
a substituted he leaving group
ring can is in
adopt the atwo
xial different
position.chair conformati
Cl
Cl
ir conformation, the leaving group occupies an E2
E2 elimination axial position. In the other chair con
elimination
can occur in this
group occupies an equatorial position. The requirement
chair conformation cannot occurfor an anti-periplanar co
hat an E2 reaction can only occur from the chair conformation in which the leaving
VIII. Regiochemical and Stereochemical Outcomes for E2
Reactions
• Which of the two molecules below will NOT be able to undergo
an E2 elimination reaction? WHY?
• It might be helpful to draw their chair structures and build a
model
Hello
VIII. Regiochemical and Stereochemical Outcomes for E2
Reactions
Rationalize the product(s) formed in the following two reactions
Hello
One
of
the
alkyl
halides
undergoes
E2
elimination
much
faster
than
it’s
diastereomer.
Why
is
there
a
difference
in
their
rxn
rates?
VIII. Regiochemical and Stereochemical Outcomes for E2
Reactions
Answers: Only
one
anti
β
hydrogen
is
H available
so
only
one
product
H can
form.
Also
the
t-‐butyl
group
wants
to
be
equatorial
Cl NOT
axial.
But
in
this
case
axial
is
required
for
the
Hello reaction
to
occur
(E2
reaction
is
slow)
(E2 reaction is fast)
Cl
There
are
two
anti
β
hydrogen’s
available
so
two
products
can
form.
Also
the
t-‐butyl
group
wants
to
be
equatorial
NOT
axial.
In
this
case
an
equatorial
t-‐Butyl
is
required
for
the
reaction
to
occur,
so
the
most
stable
chair
H H
configuration
is
required
for
the
reaction
to
occur.
VIII. Regiochemical and Stereochemical Outcomes for E2
Reactions
Predict
the
major
and
minor
products
for
each
of
the
following
E2
reactions:
a.
d.
NaOEt I NaOEt
Cl
Hello
Br
Br
b.
e.
t-BuOK
NaOEt
Br
Br
t-BuOK
c.
NaOEt
f.
VIII. Regiochemical and Stereochemical Outcomes for E2
Reactions
Answers:
There
are
many
ways
to
do
these
problems
depending
on
how
you
want
to
draw
the
intermediates.
Small
base
=
thermodynamic
product.
Large
base
generally
leads
to
the
kinetic
product
H Cl
NaOEt
a. rotate C-C bond
Hello
(Beta H and Cl anti)
H
two different
beta hydrogens
Cl to choose from
I gave two examples for H
how you can do this.
major minor
H
H Some people like this drawing better
you can clearly see that the H and Cl
are anti and the wedges are on one
C 6H 5 side of the double bond and the
Cl dashes aer on the other side.
Small
base,
can
grab
the
hard
to
get
hydrogen
which
will
form
the
thermodynamic
product.
Br Br
NaOEt
b. H
H
two different
beta hydrogens
to choose from
minor major
VIII. Regiochemical and Stereochemical Outcomes for E2
Reactions
Answers:
There
are
many
ways
to
do
these
problems
depending
on
how
you
want
to
draw
the
intermediates.
Small
base
=
thermodynamic
product.
Large
base
generally
leads
to
the
kinetic
product
Br
c.
Br
NaOEt
Hello there are multiple beta
H hydrogens, but only
one of them is anti
only
product
I NaOEt + =
d.
minor major
product
(both
are
the
same
compound)
VIII. Regiochemical and Stereochemical Outcomes for E2
Reactions
Answers:
There
are
many
ways
to
do
these
problems
depending
on
how
you
want
to
draw
the
intermediates.
Small
base
=
thermodynamic
product.
Large
base
generally
leads
to
the
kinetic
product
e. Br Br
t-BuOK
Hello Me
two different anti
H beta hydrogens
H to choose from
minor major
Br Br
t-BuOK
f. H
there are multiple beta
hydrogens, but only
Me one of them is anti
only
product
VIII. Regiochemical and Stereochemical Outcomes for E2
Reactions
• There
are
many
factors
to
consider
in
order
to
correctly
predict
the
product(s)
of
an
E2
reaction
and
decide
what
the
major
product
will
be.
Hello
– Will
the
substrate
react
stereospecifically?
or
will
it
be
a
stereoselective
E2
reaction?
– Will
the
substrate
produce
several
regioisomeric
alkenes?
If
so,
what
will
be
the
major
product,
given
the
steric
hindrance
of
the
base
that
is
used?
• The
only
way
to
master
this
material
is
to
do
lots
of
practice
problems.
End
Quiz
7a
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