SN2 Reactions of Benzylic Halides
SN2 of benzylic halides is faster than allylic halides.
How can this be explained if there is no carbocation intermediate?
University of Illinois
at Chicago
UIC
CHEM 232, Spring 2010
Slide 1
Lecture 26: April 15
1
Allylic SN2 Faster: Two Arguments
1. steric hinderance (VWF)
2. molecular orbital interactions
University of Illinois
at Chicago
UIC
•
LUMO of C-X bond can adopt a
coplanar arrangement with porbitals of p-bond =
•
electron delocalization over three
orbitals =
•
•
•
•
lower energy LUMO =
lower activation energy =
faster reaction
Why does lower energy LUMO result
in lower activation energy?
CHEM 232, Spring 2010
Slide 2
Lecture 26: April 15
2
Benzylic SN2 Faster: Two Arguments
1. steric hinderance (VWF)
2. molecular orbital interactions
Cl
University of Illinois
at Chicago
UIC
•
LUMO of C-X bond can adopt a
coplanar arrangement with porbitals of p-bond =
•
more p-orbitals in benzene than
alkene =
•
more electron donation into
LUMO of C-Cl bond =
•
•
weaker C-X bond =
faster reaction
CHEM 232, Spring 2010
Slide 3
Lecture 26: April 15
3
Preparation of Alkenylbenzenes
Same methods used to prepare alkenes can be
used to prepare alkenylbenzenes
Dehydrogenation
Dehydration
Dehydrohalogenation
University of Illinois
at Chicago
UIC
CHEM 232, Spring 2010
Slide 4
Lecture 26: April 15
4
Elimination of Benzylic Hydrogens
Addition reactions to alkenes can also be applied
to addition reactions to alkenylbenzenes
Hydrogenation
Bromination
University of Illinois
at Chicago
UIC
CHEM 232, Spring 2010
Slide 5
Lecture 26: April 15
5
Regioselective Addition of Electrophiles
to Alkenylbenzenes
Addition to alkenylbenzenes favors (faster) formation
of the more stable benzylic carbocation
University of Illinois
at Chicago
UIC
CHEM 232, Spring 2010
Slide 6
Lecture 26: April 15
6
Self Test Question
Br
What is the major regioisomeric
halohydrin formed by the
reaciton below?
Br
A
B
Br
Br
Br2, H2O
no light
0º C
OH
C
OH
Br
D
Br
E
Br
University of
Illinois at Chicago
UIC
CHEM 232, Spring 2010
Slide 7
Lecture 25: April 15
7
Self Test Question
Br
What is the major regioisomeric
halohydrin formed by the
reaciton below?
Br
A
B
Br
Br
C
Br2, H2O
no light
0º C
Br
OH
OH
δ+
δ+
Br
D
Br
Br
E
Br
University of
Illinois at Chicago
UIC
CHEM 232, Spring 2010
Slide 7
Lecture 25: April 15
7
Self Test Question
Br
What is the major regioisomeric
halohydrin formed by the
reaciton below?
Br
A
B
Br
Br
C
Br2, H2O
no light
0º C
Br
OH
OH
δ+
δ+
Br
D
Br
Br
E
Br
University of
Illinois at Chicago
UIC
CHEM 232, Spring 2010
Slide 7
Lecture 25: April 15
7
CHEM 232
Organic Chemistry I
University of Illinois
at Chicago
UIC
Lecture 26
Organic Chemistry 1
Professor Duncan Wardrop
April 15, 2010
8
Self Test Question
With respect to cyclononatetraene, which process below
will form an aromatic species?
A.
B.
C.
D.
E.
addition of one π-electron to give C9H10–
addition of two π-electrons to give C9H102–
loss of H+ from the sp3-hybridized carbon to give C9H9–
loss of H+ from an sp2-hybridized carbon to give C9H9–
loss of :H– from the sp3-hybridized carbon to give C9H9+
University of
Illinois at Chicago
UIC
CHEM 232, Spring 2010
Slide 9
Lecture 25: April 15
9
Self Test Question
With respect to cyclononatetraene, which process below
will form an aromatic species?
A.
B.
C.
D.
E.
addition of one π-electron to give C9H10–
addition of two π-electrons to give C9H102–
loss of H+ from the sp3-hybridized carbon to give C9H9–
loss of H+ from an sp2-hybridized carbon to give C9H9–
loss of :H– from the sp3-hybridized carbon to give C9H9+
University of
Illinois at Chicago
UIC
CHEM 232, Spring 2010
Slide 10
Lecture 25: April 15
10
Self Test Question
With respect to cyclononatetraene, which process below
will form an aromatic species?
2–
A.
B.
C.
D.
E.
addition of one π-electron to give C9H10–
addition of two π-electrons to give C9H102–
loss of H+ from the sp3-hybridized carbon to give C9H9–
loss of H+ from an sp2-hybridized carbon to give C9H9–
loss of :H– from the sp3-hybridized carbon to give C9H9+
University of
Illinois at Chicago
UIC
CHEM 232, Spring 2010
Slide 11
Lecture 25: April 15
11
Self Test Question
With respect to cyclononatetraene, which process below
will form an aromatic species?
A.
B.
C.
D.
E.
addition of one π-electron to give C9H10–
addition of two π-electrons to give C9H102–
loss of H+ from the sp3-hybridized carbon to give C9H9–
loss of H+ from an sp2-hybridized carbon to give C9H9–
loss of :H– from the sp3-hybridized carbon to give C9H9+
University of
Illinois at Chicago
UIC
CHEM 232, Spring 2010
Slide 12
Lecture 25: April 15
12
Self Test Question
With respect to cyclononatetraene, which process below
will form an aromatic species?
A.
B.
C.
D.
E.
addition of one π-electron to give C9H10–
addition of two π-electrons to give C9H102–
loss of H+ from the sp3-hybridized carbon to give C9H9–
loss of H+ from an sp2-hybridized carbon to give C9H9–
loss of :H– from the sp3-hybridized carbon to give C9H9+
University of
Illinois at Chicago
UIC
CHEM 232, Spring 2010
Slide 12
Lecture 25: April 15
12
Self Test Question
With respect to cyclononatetraene, which process below
will form an aromatic species?
A.
B.
C.
D.
E.
addition of one π-electron to give C9H10–
addition of two π-electrons to give C9H102–
loss of H+ from the sp3-hybridized carbon to give C9H9–
loss of H+ from an sp2-hybridized carbon to give C9H9–
loss of :H– from the sp3-hybridized carbon to give C9H9+
University of
Illinois at Chicago
UIC
CHEM 232, Spring 2010
Slide 13
Lecture 25: April 15
13
Self Test Question
With respect to cyclononatetraene, which process below
will form an aromatic species?
A.
B.
C.
D.
E.
addition of one π-electron to give C9H10–
addition of two π-electrons to give C9H102–
loss of H+ from the sp3-hybridized carbon to give C9H9–
loss of H+ from an sp2-hybridized carbon to give C9H9–
loss of :H– from the sp3-hybridized carbon to give C9H9+
University of
Illinois at Chicago
UIC
CHEM 232, Spring 2010
Slide 14
Lecture 25: April 15
14
Self Test Question
Predict the product.
A
NH2
Br
B
O
1. Br2, CH2Cl2
2. NaNH2 (excess)
3. H2O
C
4. B2H6, diglyme
5. H2O2, NaOH
D
E
University of
Illinois at Chicago
UIC
CHEM 232, Spring 2010
H
O
H
Br
OH
Slide 15
Lecture 25: April 15
15
Self Test Question
A
Predict the product.
NH2
Br
B
O
1. Br2, CH2Cl2
2. NaNH2 (excess)
3. H2O
2.
Br
Br
University of
Illinois at Chicago
UIC
3.
C
H
O
OH
4. B2H6, diglyme
5. H2O2, NaOH
1.
H
D
5.
H
4.
BH2
H
H
CHEM 232, Spring 2010
E
Br
OH
Slide 15
Lecture 25: April 15
15
Self Test Question
A
Predict the product.
NH2
Br
B
O
1. Br2, CH2Cl2
2. NaNH2 (excess)
3. H2O
2.
Br
Br
University of
Illinois at Chicago
UIC
3.
C
H
O
OH
4. B2H6, diglyme
5. H2O2, NaOH
1.
H
D
5.
H
4.
BH2
H
H
CHEM 232, Spring 2010
E
Br
OH
Slide 15
Lecture 25: April 15
15
Review: Addition Reactions to Alkenes
C C
•
•
+
δ+ δ−
E Y
E
Y
Electrophilic Addition (AdE)
In all addition reactions, the alkene is the nucleophile (Lewis base: weakly
held π-electrons are used/donated to form stronger s-bonds).
Reagent being added to the alkene is an electrophile (Lewis acid: accepting
electrons to form s-bonds).
University of Illinois
at Chicago
UIC
CHEM 232, Spring 2010
Slide 16
Lecture 26: April 15
16
Review: Addition Reactions to Alkenes
C C
+
δ+ δ−
E Y
E C C
•
•
E
Y
Y
Electrophilic Addition (AdE)
In all addition reactions, the alkene is the nucleophile (Lewis base: weakly
held π-electrons are used/donated to form stronger s-bonds).
Reagent being added to the alkene is an electrophile (Lewis acid: accepting
electrons to form s-bonds).
University of Illinois
at Chicago
UIC
CHEM 232, Spring 2010
Slide 16
Lecture 26: April 15
16
Review: Addition Reactions to Alkenes
C C
+
δ+ δ−
E Y
E
Y
variations of this mechanism
apply to different electrophiles
E C C
•
•
Y
Electrophilic Addition (AdE)
In all addition reactions, the alkene is the nucleophile (Lewis base: weakly
held π-electrons are used/donated to form stronger s-bonds).
Reagent being added to the alkene is an electrophile (Lewis acid: accepting
electrons to form s-bonds).
University of Illinois
at Chicago
UIC
CHEM 232, Spring 2010
Slide 16
Lecture 26: April 15
16
Review: Addition Reactions to Alkenes
C C
+
δ+ δ−
H Cl
H C C
•
•
H
Cl
Cl
Electrophilic Addition (AdE)
In all addition reactions, the alkene is the nucleophile (Lewis base: weakly
held π-electrons are used/donated to form stronger s-bonds).
Reagent being added to the alkene is an electrophile (Lewis acid: accepting
electrons to form s-bonds).
University of Illinois
at Chicago
UIC
CHEM 232, Spring 2010
Slide 17
Lecture 26: April 15
17
Review: Addition Reactions to Alkenes
C C
+
Br Br
Br
C C
•
•
Br
Br
Br
Electrophilic Addition (AdE)
In all addition reactions, the alkene is the nucleophile (Lewis base: weakly
held π-electrons are used/donated to form stronger s-bonds).
Reagent being added to the alkene is an electrophile (Lewis acid: accepting
electrons to form s-bonds).
University of Illinois
at Chicago
UIC
CHEM 232, Spring 2010
Slide 18
Lecture 26: April 15
18
Review: Addition Reactions to Alkenes
C C
+
H BH2
H2B
H
H2B H
•
•
Electrophilic Addition (AdE)
In all addition reactions, the alkene is the nucleophile (Lewis base: weakly
held π-electrons are used/donated to form stronger s-bonds).
Reagent being added to the alkene is an electrophile (Lewis acid: accepting
electrons to form s-bonds).
University of Illinois
at Chicago
UIC
CHEM 232, Spring 2010
Slide 19
Lecture 26: April 15
19
Review: Addition Reactions to Alkenes
C C
+
H H
H
H
H Pd
H
•
•
Electrophilic Addition (AdE)
In all addition reactions, the alkene is the nucleophile (Lewis base: weakly
held π-electrons are used/donated to form stronger s-bonds).
Reagent being added to the alkene is an electrophile (Lewis acid: accepting
electrons to form s-bonds).
University of Illinois
at Chicago
UIC
CHEM 232, Spring 2010
Slide 20
Lecture 26: April 15
20
Self Test Question
Assuming that benzene reacts similarly to alkenes,
which structure could not be an intermediate for AdE
with the general electrophile depicted?
δ+ δ−
E Y
E
B
A
University of
Illinois at Chicago
E
UIC
E
E
C
CHEM 232, Spring 2010
E
D
E
Slide 21
Lecture 25: April 15
21
Self Test Question
Assuming that benzene reacts similarly to alkenes,
which structure could not be an intermediate for AdE
with the general electrophile depicted?
δ+ δ−
E Y
E
B
A
University of
Illinois at Chicago
E
UIC
E
E
C
CHEM 232, Spring 2010
E
D
E
Slide 21
Lecture 25: April 15
21
Self Test Question
Assuming that benzene reacts similarly to alkenes,
which structure could not be an intermediate for AdE
with the general electrophile depicted?
δ+ δ−
E Y
E
B
A
University of
Illinois at Chicago
E
UIC
E
E
C
CHEM 232, Spring 2010
E
D
E
Slide 21
Lecture 25: April 15
21
Formation of Arenium Ion
•
•
•
arenium ion: carbocation formed from an aromatic
ring
formation of arenium ions is slow since the ground state
is so stable (loss of aromaticity)
requires very reactive (high energy) electrophiles
University of Illinois
at Chicago
UIC
CHEM 232, Spring 2010
Slide 22
Lecture 26: April 15
22
Arenium Ions
•
•
•
•
arenium ion: also known as a s-complex
arenium ions are allylic carbocations
stabilized by resonance
no aromatic
University of Illinois
at Chicago
UIC
CHEM 232, Spring 2010
Slide 23
Lecture 26: April 15
23
Fate of Arenium Ion
Electrophilic aromatic
substitution (SE2Ar)
Electrophilic addition (AdE2Ar)
University of Illinois
at Chicago
UIC
CHEM 232, Spring 2010
Slide 24
Lecture 26: April 15
24
Fate of Arenium Ion
Electrophilic aromatic
substitution (SE2Ar)
rearomatization
Electrophilic addition (AdE2Ar)
University of Illinois
at Chicago
UIC
CHEM 232, Spring 2010
Slide 24
Lecture 26: April 15
24
Potential Energy Diagram
University of Illinois
at Chicago
UIC
CHEM 232, Spring 2010
Slide 25
Lecture 26: April 15
25
Preparation of Electrophiles
Nitronium Ion
O N O + H2O + HSO4–
HNO3 + H2SO4
O N O
HO
O
N
O
H
+
H OH2
O
nitric acid
O
N
O
H
H
O N O
nitronium ion
University of Illinois
at Chicago
UIC
CHEM 232, Spring 2010
Slide 26
Lecture 26: April 15
26
Nitration
University of Illinois
at Chicago
UIC
CHEM 232, Spring 2010
Slide 27
Lecture 26: April 15
27
Preparation of Electrophiles
Sulfur trioxide
O
O
S
SO3 +
H2SO4
H2O
+ HSO4–
O
O
H
HO S O
O
nitric acid
+
O
H O S OH
O
H O
H
O S O
O H
O
S
O
O
sulfur trioxide
University of Illinois
at Chicago
UIC
CHEM 232, Spring 2010
Slide 28
Lecture 26: April 15
28
Sulfonation
University of Illinois
at Chicago
UIC
CHEM 232, Spring 2010
Slide 29
Lecture 26: April 15
29
Preparation of Electrophiles
Bromine
complex
University of Illinois
at Chicago
UIC
CHEM 232, Spring 2010
Slide 30
Lecture 26: April 15
30
Bromination
University of Illinois
at Chicago
UIC
CHEM 232, Spring 2010
Slide 31
Lecture 26: April 15
31
Preparation of Electrophiles
Carbocations
R X
+
AlCl3
R+
+ AlCl4–
(R = 3º or 2º)
University of Illinois
at Chicago
UIC
CHEM 232, Spring 2010
Slide 32
Lecture 26: April 15
32
Friedel-Crafts Alkylation
University of Illinois
at Chicago
UIC
CHEM 232, Spring 2010
Slide 33
Lecture 26: April 15
33
Preparation of Electrophiles
O
Acylium Ions
R C O
University of Illinois
at Chicago
R C O
UIC
R
Cl
+ AlCl3
CHEM 232, Spring 2010
R C O
+ AlCl4–
Slide 34
Lecture 26: April 15
34
Friedel-Crafts Acylation
University of Illinois
at Chicago
UIC
CHEM 232, Spring 2010
Slide 35
Lecture 26: April 15
35
Summary of Some Representative
Electrophilic Aromatic Substitutions
nitration
sulfonation
bromination
alkylation
H
HNO3, H2SO4
NO2
H
H2SO4
SO2H
H
Br2, FeBr3
Br
H
RCl, AlCl3
R
O
H
acylation
University of Illinois
at Chicago
UIC
R
O
Cl AlCl3
CHEM 232, Spring 2010
R
Slide 36
Lecture 26: April 15
36
Self Test Question
If anhydrides also react with AlCl3 to
give acylium ions, what is the product
for the acylation reaction below?
O
+
University of
Illinois at Chicago
O
AlCl3
B
O
CH3
O
OH
C
O
O
H3C
O
CH3
acetic anhydride
UIC
A
CH3
CHEM 232, Spring 2010
D
CH3
E
O
O
CH3
O
Slide 37
Lecture 25: April 15
37
Self Test Question
If anhydrides also react with AlCl3 to
give acylium ions, what is the product
for the acylation reaction below?
O
+
O
H3C
University of
Illinois at Chicago
AlCl3
UIC
CH3
O
OH
O
O
AlCl3
CH3
B
O
C
H3C
O
CH3
acetic anhydride
O
O
O
A
CH3
O
H3C C O
acylium ion
+
O
CHEM 232, Spring 2010
D
CH3
E
O
AlCl3
CH3
O
CH3
O
Slide 37
Lecture 25: April 15
37
Self Test Question
If anhydrides also react with AlCl3 to
give acylium ions, what is the product
for the acylation reaction below?
O
+
O
H3C
University of
Illinois at Chicago
AlCl3
UIC
CH3
O
OH
O
O
AlCl3
CH3
B
O
C
H3C
O
CH3
acetic anhydride
O
O
O
A
CH3
O
H3C C O
acylium ion
+
O
CHEM 232, Spring 2010
D
CH3
E
O
AlCl3
CH3
O
CH3
O
Slide 37
Lecture 25: April 15
37
Complication of Friedel-Crafts Alkylations
•
•
rearrangement to more stable carbocations always
predominates
1º alkyl chlorides (except ethyl chloride) cannot be
employed in FC alkylations
University of Illinois
at Chicago
UIC
CHEM 232, Spring 2010
Slide 38
Lecture 26: April 15
38
Reduction of Aryl Ketones
Clemmensen Reduction
O
Zn(Hg)
HCl
Wolf-Kishner Reduction
O
H2NNH2, KOH
University of Illinois
at Chicago
UIC
CHEM 232, Spring 2010
Slide 39
Lecture 26: April 15
39
Alternative Strategy to Alkybenzenes
O
R
University of Illinois
at Chicago
UIC
O
R
CHEM 232, Spring 2010
+
Cl
R
Slide 40
Lecture 26: April 15
40
Alternative Strategy to Alkybenzenes
methylene group (CH2)
O
R
University of Illinois
at Chicago
UIC
O
R
CHEM 232, Spring 2010
+
Cl
R
Slide 40
Lecture 26: April 15
40
Self Test Question
CN
A
N
Predict the product.
O
B
N
CN
Br
1. benzene, AlCl3
2. Zn(Hg), HCl
O
N
Cl
CN
C
3. NBS, CHCl3
4. NaCN
N
CN
Br
D
University of
Illinois at Chicago
UIC
CHEM 232, Spring 2010
N
Slide 41
Lecture 25: April 15
41
Self Test Question
CN
A
N
Predict the product.
O
B
N
CN
Br
1. benzene, AlCl3
2. Zn(Hg), HCl
O
N
1.
Cl
CN
C
3. NBS, CHCl3
4. NaCN
4.
N
University of
Illinois at Chicago
CN
Br
O
2.
UIC
N
3.
N
CHEM 232, Spring 2010
N
Br
D
N
Slide 41
Lecture 25: April 15
41
Self Test Question
CN
A
N
Predict the product.
O
B
N
CN
Br
1. benzene, AlCl3
2. Zn(Hg), HCl
O
N
1.
Cl
CN
C
3. NBS, CHCl3
4. NaCN
4.
N
University of
Illinois at Chicago
CN
Br
O
2.
UIC
N
3.
N
CHEM 232, Spring 2010
N
Br
D
N
Slide 41
Lecture 25: April 15
41
CHEM 232
Organic Chemistry I
University of Illinois
at Chicago
UIC
Next Lecture...
Chapter 12: Sections 12.9-12.13
Quiz Next Week. . .
Synthesis Problem
Chapters 11 & 12
42