1
1
Which is aromatic?1. 1
2. 2
3. 3
4. 4
How many are aromatic?
Assume all are planar.
Note: all formal chargesare shown, but notlone pairs.
A
2
Which is aromatic?14 aromatic pi electrons
Select the aromatic one(s)
B (like Al)relatively stable w/ sextet of valence electrons
B sp2 hybridized
A
all atoms possess pure p-orbital (continuous p-system)
the other p bond is
one p bond is w/ aromatic p-systemn
X
3
©Dr. Kay Sandberg
Last lecture
This lecture
Reactions of benzene derivatives
Aromaticity
Birch Reduction
Free-radical substitution (via NBS) review
What makes a system aromatic
Alkenylbenzene reactions
Benzylic chemistry
4
© Kay Sandberg
Regioselectivity of free-radical halogenation
3 2
1
65
4 C
H
H
HH
H
H H
Section 11.12
3 2
1
65
4 C
H
H
HH
H
H H
d
d
dd
3 2
1
65
4 C
H
H
HH
H
H H
H Br
BrH
Radical character
shared by
benzylic,
ortho & para carbons
5
N
O
O
Br
(N-bromosuccinimide)
© Kay Sandberg
Regioselectivity of free-radical halogenation
Br3 2
1
65
4 C
H
H
HH
H
H H
NBS
NBS Regioselectivie reagent
for allylic (chap 10) and benzylic (chap 11)
bromination.6
© Kay Sandberg
3 2
1
65
4 C
H
H
HH
H
H H
Section 11.12
d
d
d
d
Br
LQ #1) Draw the substitution product that would
result if the Br bonded to the para carbon
instead of the benzylic carbon.
Even though we can draw this product on paper,
it never forms in the flask. Do you know why you
should never propose this as a major product?
Radical character shared by
benzylic, ortho & para carbons
2
7
Oxidation numbers
Section 11.13
Na2Cr2O7
H2O, H2SO4, heat
© Kay Sandberg
KMnO4
H2O, heat
Cr2O72-
-2x 7
-14+ = -2+12
x 2
+6
Cr(VI)
Oxidation: benzene derivatives
8
Mn(VII)
1. 2. 3. 4. 5. 6. 7. 8.
0% 0% 0% 0%0%0%0%0%
1. 1
2. 2
3. 3
4. 4
5. 5
6. 6
7. 7
8. 8
Section 11.13
Na2Cr2O7
H2O, H2SO4, heat
© Kay Sandberg
KMnO4
H2O, heat
Cr2O72-
-2x 7
-14+ = -2+12
x 2
+6
Cr(VI)
Oxidation: benzene derivatives
Click Manganese’s ox #
10
9
Alkane & benzene
Section 11.13
RR'
RCH2CH2R'
Na2Cr2O7
H2O, H2SO4, heat
© Kay Sandberg
Na2Cr2O7
H2O, H2SO4, heat
Oxidation: alkylbenzene
No reaction
No reaction
10
Alkylbenzene oxidation
Section 11.13
© Kay Sandberg
Na2Cr2O7
H2O, H2SO4, heat
C
R
HH
Oxidation: alkylbenzene
C
O
OH
C
O
OH
O2N
C
O
OH
C
O
HO
CH3O2N1. KMnO4, H2O,
2. H2O, H+
CH3CH
CH3
CH3
Na2Cr2O7
H2O, H2SO4, heat
CH3C
CH3
CH3
CH3
Na2Cr2O7
H2O, H2SO4, heat
C
O
OH
C
CH3
CH3
CH3
benzoic acid
11
Toluene vs benzene
Section 11.13
© Kay Sandberg
liver enzymeC
H
HH
O2
cytochrome P-450
Oxidation: alkylbenzene
C
O
OH
Toluenewater insoluble
Benzoic acidwater soluble
liver enzyme
O2
cytochrome P-450o
carcinogen12
Oxidation reagent flash cards
Section 11.13 © Kay SandbergOxidation: alkylbenzene
C
O
OH
Benzoic acid
1. KMnO4, H2O
2. acid workup
C
O
OH
Benzoic acid
Na2Cr2O7
H2O, H2SO4
C
H
HR
C
R'
HR
C
methyl, 1o, 2o benzylic carbons possess benzylic H
1o benzylic C
2o benzylic C
3
13
Benzylic reactions
NBS
© Kay Sandberg
C
H
HH C
O
OH
TolueneBenzoic acid
KMnO4
Benzylic bromide
Na2Cr2O7
H2O, H2SO4
C
R'
HR
C
Reactions involving a benzylic radical intermediate.
2o benzylic C (or toluene or 1o benzylic)
peroxide
C
Br
R'R
14
3 2
1
65
4 C
H
H
HH
H
H H
3 2
1
65
4 C
H
H
HH
H
H H
©Dr. Kay Sandberg
C
C
C
H
H
H
H
H
d
d
dd
Allylic radical vs benzylic radical
Alike in that both are stabilized by resonance.
Different in that substitution can occur at all
radical character carbons of allylic system,
compared to only at benzylic position.
d d
C
C
C
H
H
H
H
H
15
C
C
C
H
H
H
H
H
©Dr. Kay Sandberg
C
C
C
H
H
H
H
H
3 2
1
65
4 C
H
H
HH
H
H H
Allylic cation vs benzylic cation
Alike in that both are stabilized by resonance.
Different in that substitution can occur at all
positive character carbons of allylic system,
compared to only at benzylic position?
d+ d+ d+
d+
d+
d+
3 2
1
65
4 C
H
H
HH
H
H H
16
© Kay Sandberg
Section 10.2Allylic carbocations: Rates of solvolysis
C C
C
H3C
CH3
H
H
H
3o Allylic cation
C C
C Cl
H3C CH3
H
H
H
H3C
C Cl
H3C CH3
H3C
C
H3C
CH3
3o carbocation
H
O
H
O
100 x faster
SN1
SN1
17
© Kay Sandberg
Section 11.14Benzylic carbocations: Rates of solvolysis
C
H3C
CH3
3o benzylic cation
C Cl
H3C CH3
H
O
600 x faster
SN1
H3C
C Cl
H3C CH3
H3C
C
H3C
CH3
3o carbocation
H
O
SN1
18
- +
© Kay SandbergSection 11.14
Stability of benzyl cation
C
H
H
3 2
1
65
4 C
H
H
3 2
1
65
4 C
H
H
3 2
1
65
4 C
H
H
Resonance delocalized:
benzylic
ortho
para
ortho
ROY G B
4
19
© Kay Sandberg
Section 11.14Stability of benzyl cation
Resonance delocalized:
C
H
H
3 2
1
65
4 C
H
H
3 2
1
65
4 C
H
H
3 2
1
65
4 C
H
H
benzylic
ortho
para
ortho
C
H
H
d+d+
d+
d+
20
Orbital description of benzylic cation
© Kay Sandberg
Section 11.14Stabilization due to overlap of
benzylic pure p orbital
with the extended p system of ring
Benzyl cation
21
© Kay Sandberg
EC C
C
R
R
H
H
H
R
C
R
R
R
C
R
H
R
C
H
H
H
C
H
H
CH H2C vinyl cation (least stable)
allylic cation
carbocation stabilities
C C
C
R
R
C
H
C
CC
H
HH
H benzylic cation (most stable)
22
C C
C
H3C
CH3
H
H
H
O
C C
C
H3C
CH3
H
H
H
d+
d+
© Kay Sandberg
Section 10.2Allylic carbocations: Rates of solvolysis
C C
C
H3C
CH3
H
H
H
Allylic cation:
C C
C Cl
H3C CH3
H
H
H
HO
SN1 C C
C
H3C
CH3
H
H
H
C C
C
H3C
CH3
H
H
HO
PT
HO
PT
23
© Kay Sandberg
Section 11.14
Benzylic cation
C
H3C
CH3
C Cl
H3C CH3
H
OSN1
C d+d+
d+
d+
OH
24
© Kay Sandberg
Section 11.14
H
O
C
H3C
CH3
O CH2
CH3
-H+ (PT)
still aromatic
C d+d+
d+
d+
C
H3C
CH3
O
-H+ (PT)
C
HO
LQ #2) Draw product resulting
from attack of the ortho C.
C
H3C
CH3
O H H
HH
H
Again, you would never propose
this to be a product in practice.
5
25
© Kay Sandberg
Section 11.14Unlike allylic halides where nucleophilic
attack occurs at different carbons bearing
a partial positive charge, benzylic halides
only give one substitution product.
Benzyl cation
C
H3C
CH3
C Cl
H3C CH3
H
OSN1
C
H3C
CH3
O CH2
CH3
-H+
Attack at ortho or
para positions would
destroy aromaticity
Only
substitution
product
C d+d+
d+
d+
26
Birch reduction “What”
© Kay Sandberg
Section 11.11Birch Reduction
arene reduced to nonconjugated
diene
Na, NH3
CH3OH
Whoa! What can make an aromatic
ring give up aromaticity?
If being aromatic is great, is there anything that can destroy aromaticity?
27
Na (s), NH3 past reaction
© Kay Sandberg
Section 9.10Alkenes from alkynes:
Metal-ammonia reduction of alkynes
Na
NH3H
H
3-hexyne
Stereoselective for trans-stereoisomer
(E)-3-hexene
Lindlar Pd
H2
3-hexyne(Z)-3-hexene
Stereospecific for cis-stereoisomer
H H28
Birch reduction “Why”
+ 2Na + 2CH3OH
H
H
H
H
H
HHH
H H
H
H
H
H
NH3
NaNa
© Kay Sandberg
Section 11.11Birch Reduction
arene reduced to nonconjugated
diene
Na
Na
CH3O-H
CH3O-H
CH3O
CH3O
29
Birch reduction “How”
© Kay Sandberg
Section 11.11Birch Reduction
arene reduced to nonconjugated
diene
+ 2Na + 2CH3O
+ 2Na + 2CH3OH
H
H
H
H
H
HHH
H H
H
H
H
H
NH3
4 step process:
Step 1: electron transfer
Step 2: proton transfer
Step 3: electron transfer
Step 4: proton transfer30
Step 1
© Kay Sandberg
Section 11.11Na
Birch Reduction
6 p electrons
NaRadical anion
Step 1: electron transfer
H
H
H
H
Observed MOP
6
31
Step 2
HH
H
H H
H
H
Step 2: proton transfer
HO
CH3
© Kay SandbergSection 11.11Birch Reduction
H
HH
H
H
H
HH
H
H H
H
H
OCH3
32
Step 3
HH
H
H H
H
H
© Kay Sandberg
Section 11.11Birch Reduction
Na
Step 3: electron transfer
H
H
H
H
Observed MOP
33
MO’s
© Kay SandbergSection 11.11
p1
side
view
top
view
A B C D E
E
p2
p3
p4
p5 5 p-electrons
5 p-orbitals
H
H
H
H
H
34
Which is p3?
1. 2. 3. 4. 5.
0% 0% 0%0%0%
1. A
2. B
3. C
4. D
5. E
© Kay SandbergSection 11.11
p1
side
view
top
view
A B C D E
E
p2
p3
p4
p5 5 p-electrons
5 p-orbitals
H
H
H
H
H10
35
SOMO
© Kay Sandberg
Section 11.11Birch Reduction
HH
H
H H
H
H
ESOMO
NaH
H
H
H H
H
H
36
Step 3, again
HH
H
H H
H
H
© Kay Sandberg
Section 11.11Birch Reduction
Na
HH
H
H H
H
H
Na
Step 3: electron transfer
HH
H
H H
H
H
H H
H
H H
H
H
7
37
Step 4
© Kay Sandberg
Section 11.11Birch Reduction
H H
H
H H
H
HHO
H3C
H H
H
H H
H
HH
Step 4: proton transfer
OCH3
38
CH3
H
H
H
H
H
H
H
Birch reduction of toluene
© Kay Sandberg
Section 11.11
CH3 CH3
Na Na Na Na
Birch Reduction of toluene
LUMO
CH3
H
H
H
H
H
H
CH3
H
H
H
H
H
H
39
1. A
2. B
CH3
MOP Birch w/toluene
1. 2.
0%0%
© Kay Sandberg
Section 11.11
CH3
Na Na Na Na
Birch Reduction of toluene
LUMO
A B10
40
CH3
© Kay Sandberg
Section 11.11Birch Reduction of toluene
LUMO
CH3
Na Na Na Na
41
Birch reduction of benzoic acid
© Kay Sandberg
Section 11.11Birch Reduction of benzoic acid
LUMO
MOP
Largest probability
volumes
O
OH
LQ #3
42
Electron donors vs withdrawers
© Kay Sandberg
Section 11.11
CH3
O
OH
alkyl groups
donate e- density
e- pump
carbonyl groups
withdraw e- density
e- vacuum
e- donor e- withdrawer
8
43
Birch reduction of benzoic acid MOP
© Kay Sandberg
Section 11.11
Na
O
OH
O
OH
O
OH
d+
d-O
OH
O
OH
MOP
Na
44
Birch reduction of alkylbenzene MOP
e- pumps end up bonded to one of the double bonds.
X X
© Kay Sandberg
Section 11.11
Na
MOP
Na
HH
H
H
H
HH
Na
45
Birch reduction MOP prediction
© Kay Sandberg
Section 11.11Birch Reduction:
2Na, NH3
2CH3CH2OHp-dipropylbenzene
LQ #4
MOP
46
Which C?
1. 1
2. 2
3. 3
4. 4
5. 5
6. 6
7. 7
8. 8
Electrophilic addition of HX
Click the letter of the C that
will end up bonded to the H.
47
© Kay Sandberg
Section 11.16Reactions of alkenylbenzenes: addition
HX
regioselective
b
aCl
H
HCl
b
aH Cl
b
aH Cl
b
aCl
H
H
Cl
Benzylic cation: more stable
faster
slower48
© Kay Sandberg
Section 11.16
HBr
Reactions of alkenylbenzenes: addition
regioselectiveHX
H
Br
Anti-Markovnikov addition
HBr
peroxides
H
Br
Markovnikov addition
In both cases
the more stable
intermediate is
formed faster.
9
49
Section 11.14
© Kay Sandberg
CH3CO2-Na
+
C
H
HCl
O2NCH3CO2H
Nucleophilic Substitution: benzylic halides
CH2O2N
C
O
O
CH3
1o benzylic halide
Competitive elimination product?
Substitution product
No b-H therefore cannot undergoelimination.
C
O
O
H3C
50
Section 11.14 © Kay Sandberg
CH
CH2
2o benzylic halide
CH3CH2O-Na
+
C
H
H3CCl
CH3CH2OH
C
H
H3CCl NaI
acetone
Strong base
Weak base
C
H
H3CI
styrene
Great nucleophile
Good nucleophile
E2
SN2
SN1?
51
CH
OH
CH3
Cl
H2SO4
heatCH
CH2
Cl
© Kay Sandberg
Section 11.15Preparation of alkenylbenzenes
dehydation
630o
ZnO
dehydrogenation
NaOCH2CH3
HOCH2CH3, heat
Br
dehydrohalogenation benzylic Br
styrene
52
1. top, purple
2. bottom, blue
MOP
© Kay Sandberg
Section 11.15Preparation of alkenylbenzenes
NaOCH2CH3
HOCH2CH3, heat
Br
MOP
2o
SN2 SN1 E2 E1O
O
Strong base
1
2Conjugated
Isolated
53
C C
H
H
H
C C
H
H
OR
H
© Kay Sandberg
+C C
H
H
H
OR C C
H
H
OR
H
C C
H
H
OR
H
C
H
C
H
H
Section 11.17Polymerization of styrene
