Post on 01-Apr-2015
transcript
Created byProfessor William Tam & Dr. Phillis
Chang Ch. 15 - 1
Chapter 15Chapter 15
Reactions ofReactions ofAromatic CompoundsAromatic Compounds
Ch. 15 - 2
1. Electrophilic AromaticSubstitution Reactions
Overall reaction:
H E
H+E++
Ch. 15 - 3
X
X2
FeX3
NO2
HNO3
H2SO4
R
RClAlCl3
R
O R Cl
O
AlCl3
SO3H
H2SO4
SO3
Ch. 15 - 4
2. A General Mechanism for Electro-philic Aromatic Substitution
Different chemistry with alkene.
C
CBr2
Br C
C Br
Br2
+
+ No Reaction
Ch. 15 - 5
Benzene does not undergo electrophilic addition, but it undergoes electrophilic aromatic substitution.
+
HE A
H A
E
(H substituted by E)
Ch. 15 - 6
Mechanism●Step 1:
E+ E
slowr.d.s.
E
E
Ch. 15 - 7
E
H
B
Mechanism●Step 2:
E
B H+fast
Ch. 15 - 8
Energy Profile for EAS:
Ch. 15 - 9
3. Halogenation of Benzene
Benzene does not react with Br2 or Cl2 unless a Lewis acid is present (catalytic amount is usually enough) and the reaction typically requires heat.
Ch. 15 - 10
Examples:Cl
HClCl2
+FeCl325o
(90%)
Br
HBrBr2
+FeCl3heat
(75%)
●Reactivity: F2 > Cl2 > Br2 > I2
Ch. 15 - 11
Mechanism:
Br Br
FeBr3
(weakelectrophile)
Br Br FeBr3
Br + FeBr4
(very reactiveelectrophile)
Ch. 15 - 12
BrBrBr
Brslow r.d.s.
Mechanism (Cont’d):
Ch. 15 - 13
Mechanism (Cont’d):
Br
HBr FeBr3 Br
Br H+
+ FeBr3
Ch. 15 - 14
F2: too reactive, give mixture of mono-, di- and highly substituted products.
F F F
F
F
+ +
+ others
F2Lewisacid
Ch. 15 - 15
I2: very unreactive even in the presence of Lewis acid, usually need to add an oxidizing agent (e.g. HNO3, Cu2+, H2O2).
II2
HNO3(86%)
e.g.
I
(65%)I2
CuCl2
Ch. 15 - 16
4. Nitration of Benzene
Electrophile in this case is NO2
(nitronium ion).
conc. HNO3NO2
+ H3O+
+ HSO4
conc. H2SO4
50-60oC (85%)
Ch. 15 - 17
Mechanism:
O
S
O
OHO H N
O
O
HO+
HSO4 N
O
O
O
H
H
+ N OO H2O
(NO2)
+
Ch. 15 - 18
NO2slow r.d.s.
NO2NO2NO2
Mechanism (Cont’d):
Ch. 15 - 19
Mechanism (Cont’d):
NO2
HH2O NO2
+ H3O+
Ch. 15 - 20
5. Sulfonation of Benzene Mechanism
●Step 1:+ +2 H2SO4 SO3 H3O
+ HSO4
●Step 2:O
SO O
H
SO
O
O
slow
otherresonancestructures
Ch. 15 - 21
H
SO
O
O
HSO4
fastS
O
O
O
+ H2SO4
●Step 3:
●Step 4:
S
O
O
O
H O
H
H
fast
+ H2O
S
O
O
O H
Ch. 15 - 22
SO3H
SO3, conc. H2SO4 (oleum)
25oC - 80oC
Sulfonation & Desulfonation:
dil. H2SO4
H2O, 100oC
This is the only reversible EAS reaction.
Ch. 15 - 23
6. Friedel–Crafts Alkylation
R XR
HXLewis acid(e.g. AlCl3)
+
R = alkyl group(not aryl or vinyl)
Electrophile in this case is R.●R = 2o or 3o
●Or (R = 1o)R ClAlCl3
Ch. 15 - 24
Mechanism:
Cl AlCl3 Cl AlCl3
AlCl4+
Ch. 15 - 25
Mechanism (Cont’d):
Ch. 15 - 26
Mechanism (Cont’d):
HCl AlCl3
+ HCl
+ AlCl3
Ch. 15 - 27
Note: It is not necessary to start with an alkyl halide, other possible functional groups can be used to generate a reactive carbocation.
+ H+
e.g.
H+via
Ch. 15 - 28
OH
BF3
60oC+
O BF3
Hvia
Examples:
Ch. 15 - 29
7. Friedel–Crafts Acylation
O
R Cl
R
O
+AlCl3
80oC
Acyl group:R C
O
Electrophile in this case is R–C≡O (acylium ion).
Ch. 15 - 30
Mechanism:
O
R ClAlCl3+
R C O R C O
O
CR Cl AlCl3
Ch. 15 - 31
Mechanism (Cont’d):
R C O
R
O
R
O
R
O
Ch. 15 - 32
Mechanism (Cont’d):
H
O
RCl AlCl3
+ HCl
+ AlCl3
R
O
Ch. 15 - 33
Acid chlorides (or acyl chlorides)
RC
O
Cl
RC
O
OH RC
O
Clor
SOCl2
PCl5
●Can be prepared by:
Ch. 15 - 34
8. Limitations of Friedel–CraftsReactions
When the carbocation formed from an alkyl halide, alkene, or alcohol can rearrange to one or more carbocations that are more stable, it usually does so, and the major products obtained from the reaction are usually those from the more stable carbocations.
Ch. 15 - 35
(How is thisFormed?)
(not formed) For example:
AlCl3Cl+
AlCl3
Ch. 15 - 36
1o cation (not stable)
Reason:
Cl AlCl3
HAlCl4+ +
1,2-hydride shift
H 3o cation(more stable)
Ch. 15 - 37
Friedel–Crafts reactions usually give poor yields when powerful electron-withdrawing groups are present on the aromatic ring or when the ring bears an –NH2, –NHR, or –NR2 group. This applies to both alkylations and acylations, i.e. these do not work.NO2
>
N(CH3)3
> > >
CF3
>
SO3H
>
NH2O OH O R
These usually give poor yields in Friedel-Crafts
reactions
Ch. 15 - 38
The amino groups, –NH2, –NHR, and –NR2, are changed into powerful electron-withdrawing groups by the Lewis acids used to catalyze Friedel-Crafts reactions.
N NH H
H
H AlCl3
>
AlCl3+
Does not undergo a
Friedel-Crafts reaction
Ch. 15 - 39
Aryl and vinylic halides cannot be used as the halide component because they do not form carbocations readily.
, AlCl3
Cl
Cl , AlCl3
No Friedel-Craftsreaction
No Friedel-Craftsreaction
sp2
sp2
Ch. 15 - 40
Polyalkylations often occur:
+OH
+BF3
60oC
(24%) (14%)
Ch. 15 - 41
9. Synthetic Applications ofFriedel-Crafts Acylations: The Clemmensen Reduction
Clemmensen ketone reduction:
HClreflux
R
O
RZn/Hg
Ch. 15 - 42
Clemmensen ketone reduction●A very useful reaction for
making alkyl benzene that cannot be made via Friedel-Crafts alkylations.
?
e.g.
Ch. 15 - 43
Clemmensen ketone reduction●Cannot use Friedel-Crafts
alkylation.
Cl
AlCl3
give
butNOT
Ch. 15 - 44
Rearrangements of carbon chain do not occur in Friedel-Crafts acylations.
O
R Cl
R
O
+AlCl3
80oC
(no rearrangement of
the R group)
Ch. 15 - 45
Cl
AlCl3
OO Zn/Hg
conc. HClreflux
FC Acylation followed by Clemmenson.
Ch. 15 - 46
10.Substituents Can Affect Boththe Reactivity of the Ring and the Orientation of the Incoming Group
Two questions need to be addressed when the ring already has a substituent:●Reactivity toward EAS●Regiochemistry of products
Ch. 15 - 47
●Reactivity:Y Y
E
E
faster or slower than E
E
Y = EDG (electron-donating group) or EWG (electron-withdrawing group).
Ch. 15 - 48
●Regiochemistry:Y
E
Y Y Y
E
E
E(ortho)
(o)(meta)
(m)(para)
(p)
Statistical mixture of o-, m-, p- products or any preference?
Ch. 15 - 49
G
E A+
GE
Hotherresonancestructure
A substituted
benzene
Electrophilic reagent Areniu
m ion
Ch. 15 - 50
Z> Y
>
Y withdraws electrons
Z donates electrons
The ring is electron poor
and reacts more slowly with an electrophile
The ring is more electron rich and reacts faster with an electrophile
Ch. 15 - 51
●Reactivity: Since electrophilic aromatic
substitution is electrophilic in nature, and the r.d.s. is the attack of an electrophile (E) with the benzene -electrons, an increase in e⊖ density in the benzene ring will increase the reactivity of the aromatic ring towards attack of an electrophile, and result in a faster reaction.
Ch. 15 - 52
●Reactivity:
On the other hand, decrease in e⊖ density in the benzene ring will decrease the reactivity of the aromatic ring towards the attack of an electrophile, and result in a slower reaction.
Ch. 15 - 53
Y
EDG
–H
EWGIncr
easi
ng a
ctiv
ity
●Reactivity:
Ch. 15 - 54
●Reactivity:
EDG (electron-donating group) on benzene ring: Increases electron
density in the benzene ring.
More reactive towards electrophilic aromatic substitution.
Ch. 15 - 55
●Reactivity:
EWG (electron-withdrawing group) on benzene ring: Decreases electron
density in the benzene ring.
Less reactive towards electrophilic aromatic substitution.
Ch. 15 - 56
●Reactivity towards electrophilic aromatic substitution.
EDG EWG
> >
Ch. 15 - 57
Regiochemistry: the directing effect
●General aspects: Substituents are either o-, p-
directing or m-directing. The rate-determining-step is
due to -electrons of the benzene ring attacking an electrophile (E).
Ch. 15 - 58
orthoattack
YYY
o-I o-II o-III
EEE
Y
E
Ch. 15 - 59
metaattack
YYY
m-I m-II m-IIIE E E
Y
E
Ch. 15 - 60
paraattack
p-I p-II p-III
YYY
E E E
Y
E
Ch. 15 - 61
If you look at these resonance structures closely, you will notice that for ortho- or para-substitution, each has one resonance form with the positive charge attached to the carbon that directly attached to the substituent Y (o-I and p-II).
Y
E
Y
Ep-II
o-I
Ch. 15 - 62
When Y = EWG, these resonance forms (o-I and p-II) are highly unstable and unfavorable to form, thus not favoring the formation of o- and p- regioisomers, and m- product will form preferentially.
Ch. 15 - 63
On the other hand, if Y = EDG, these resonance forms (o-I and p-II) are extra-stable (due to positive mesomeric effect or positive inductive effect of Y) and favorable to form, thus favoring the formation of o- and p- regioisomers.
Ch. 15 - 64
Classification of different substituents:Y
Y (EDG)
–NH2, –NR2
–OH, –OStrongly activating
o-, p-directing
–NHCOR–OR
Moderately activating
o-, p-directing
–R (alkyl)–Ph
Weakly activating
o-, p-directing
–H NA NA
Ch. 15 - 65
Classification of different substituents:Y
Y (EWG)
–Halide(F, Cl, Br, I)
Weakly deactivating
o-, p-directing
–COOR, –COR,–CHO, –COOH,–SO3H, –CN
Moderately deactivating
m-directing
–CF3 , –CCl3 ,–NO2 , –⊕NR3
Strongly deactivating
m-directing
Ch. 15 - 66
11.How Substituents AffectElectrophilic AromaticSubstitution: A Closer Look
Ch. 15 - 67
If G is an electron-releasing group (relative to hydrogen), the reaction occurs faster than the corresponding reaction of benzene
11A. 11A. Reactivity: Reactivity: The Effect of The Effect of Electron-Releasing and Electron-Releasing and Electron-Withdrawing GroupsElectron-Withdrawing Groups
E+
G>
H E
G>
H E
G>
G releaseselectrons.
Transition stateis stabilized
Arenium ionis stabilized
When G is electron donating,the reaction is faster.
Ch. 15 - 68
If G is an electron-withdrawing group, the reaction is slower than that of benzene.
E+
G
>
H E
G
>
H E
G
>
G withdrawselectrons
Transition stateis destabilized
Arenium ionis destabilized
When G is electron withdrawing, the reaction is slower.
Ch. 15 - 69
Energy Profiles for these Cases:EWG EDGNo Substituent
Ch. 15 - 70
Two types of EDG(i)
11B. 11B. Inductive and Resonance Effects:Inductive and Resonance Effects: Theory of OrientationTheory of Orientation
(donates electron towards the benzene ring through resonance effect)
OR NR2
or
CH3>(ii) by positive inductive effect (donates electron towards the benzene ring through bond)
Ch. 15 - 71
Two types of EDG
●The resonance effect is usually stronger than positive inductive effect if the atoms directly attacked to the benzene ring is in the same row as carbon in the periodic table
Ch. 15 - 72
Similar to EDG, EWG can withdraw electrons from the benzene ring by resonance effect or by negative inductive effect.
C
O
CH3e.g.
>
C F
F
F
>
Deactivate the ring by resonance effect
Deactivate the ring by negative inductive effect
Ch. 15 - 73
EWG = –COOR, –COR, –CHO, –CF3, –NO2, etc.
11C. 11C. Meta-Directing GroupsMeta-Directing Groups
EWG EWG
E
E
(major)
(EWG ≠ halogen)
Ch. 15 - 74
For example:
CF3 CF3CF3
NO2NO2NO2
CF3
NO2
(ortho)
CF3
NO2- H+
(ortho)
(not favorable)
(highly unstable due to negative inductive effect of –CF3)
Ch. 15 - 75
CF3 CF3CF3
CF3
NO2
CF3
NO2
NO2 NO2 NO2
- H+
(para)
(para)(not favorable)
(highly unstable due to negative inductive effect of –CF3)
Ch. 15 - 76
CF3 CF3CF3
- H+
CF3
NO2 NO2 NO2
NO2
CF3
NO2
(meta)
(relatively more favorable than o-, p- products)
(meta)
(positive charge never attaches to the carbon directly attached to the EWG: –CF3) relatively more favorable.
Ch. 15 - 77
EDG = –NR2, –OR, –OH, etc.
11D. 11D. OrthoOrtho––Para-Directing GroupsPara-Directing Groups
EDG EDG
E
(major)
E
EDG
E
+
ortho para
Ch. 15 - 78
OCH3
OCH3
NO2
OCH3
NO2
OCH3
NO2
OCH3
NO2
OCH3
NO2
NO2
(ortho)
- H+
(ortho)(favorable)
For example:
(extra resonance structure due to –OCH3).
Ch. 15 - 79
OCH3 OCH3OCH3
OCH3
OCH3
(para)
NO2 NO2NO2
NO2
- H+
OCH3
NO2
(para)(favorable)
NO2
(extra resonance structure due to –OCH3)
Ch. 15 - 80
OCH3 OCH3OCH3
OCH3
NO2
(meta)
- H+
OCH3
NO2 NO2 NO2
NO2
(meta)(less favorable)
(3 resonance structures only, no extra stabilization by resonance with –OCH3) less favorable.
Ch. 15 - 81
For halogens, two opposing effects:
negative inductive effect withdrawing
electron density from the
benzene ring
ClCl
>
resonance effect from –Cl donating
electrondensity to thebenzene ring
Ch. 15 - 82
Overall:●Halogens are weak
deactivating groups. Negative inductive effect >
resonance effect in this case)
Ch. 15 - 83
Cl
Cl
NO2
Cl
NO2
Cl
NO2
Cl
NO2
Cl
NO2
NO2
(ortho)
- H+
(ortho)(favorable)
Regiochemistry:
(extra resonance structure due to resonance of –Cl).
Ch. 15 - 84
Cl ClCl
Cl
Cl
(para)
NO2 NO2NO2
NO2
- H+
Cl
NO2
(para)(favorable)
NO2
(extra resonance structure due to resonance of –Cl).
Ch. 15 - 85
Cl ClCl
Cl
NO2
(meta)
- H+
Cl
NO2 NO2 NO2
NO2
(meta)(less favorable)
(3 resonance structures only, no extra stabilization by resonance effect of –Cl) less favorable.
Ch. 15 - 86
11E. 11E. OrthoOrtho––Para Direction andPara Direction and Reactivity of AlkylbenzenesReactivity of Alkylbenzenes
E+
R>
H E
R>
H E
R>
Transition stateis stabilized
Arenium ionis stabilized
Ch. 15 - 87
CH3
E
CH3
E
CH3
E
CH3
E
>
Ortho attack:
Relatively stable contributor
Ch. 15 - 88
CH3
E
CH3 CH3 CH3
EEE
Meta attack:
Ch. 15 - 89
CH3
E
CH3 CH3 CH3
E E E
>
Para attack:
Relatively stable contributor
Ch. 15 - 90
12.Reactions of the Side Chainof Alkylbenzenes
CH3
Methylbenzene(toluene)
Ethylbenzene Isopropylbenzene(cumene)
Phenylethene(styrene or
vinylbenzene)
Ch. 15 - 91
12A. 12A. Benzylic Radicals and CationsBenzylic Radicals and Cations
Methylbenzene(toluene)
CH2HR
- RH
CH2
The benzylradical
CC C C
Benzylic radicals are stabilized by resonance.
Ch. 15 - 92
C
- LG
C
A benzylcation
LG
CC C C
Benzylic cations are stabilized by resonance.
Ch. 15 - 93
12B. 12B. Halogenation of the Side Chain:Halogenation of the Side Chain: Benzylic RadicalsBenzylic Radicals
light
Benzyl bromide(-bromotoluene)
(64%)
CH3
N
O
O
BrBr
N
O
O
HCCl4
+ +
NBS
N-Bromosuccinimide (NBS) furnishes a low concentration of Br2, and the reaction is analogous to that for allylic bromination.
Ch. 15 - 94
Mechanism●Chain initiation:
2 XX Xperoxides
heat orlight
●Chain propagation:
X
H
CC6H5 H
H
+
H
CC6H5
H
H X+
Ch. 15 - 95
●Chain propagation:
●Chain termination:
X
H
CC6H5 X
H
+
H
CC6H5
H
+X X
X
H
CC6H5 X
H
+
H
CC6H5
H
Ch. 15 - 96
e.g.
NBS
h
(more stable benzylic radicals)
(less stable 1o radicals)
Br
+
Br
(major) (very little)
Ch. 15 - 97
13.Alkenylbenzenes
C C
C
C
C C
conjugatedsystem
non-conjugatedsystem
is morestable than
13A. 13A. Stability of Conjugated Alkenyl-Stability of Conjugated Alkenyl- benzenesbenzenes
Alkenylbenzenes that have their side-chain double bond conjugated with the benzene ring are more stable than those that do not.
Ch. 15 - 98
Example:
H+
heatOH
(not observed)
Ha Hb
- Ha
- Hb
Ch. 15 - 99
13B. 13B. Additions to the Double Bond ofAdditions to the Double Bond of AlkenylbenzenesAlkenylbenzenes
HBr
RO ORheat
HBr
(noperoxides)
Br
Br
Ch. 15 - 100
Mechanism (top reaction):2 RORO OR
H Br+RO Br RO H+
+ BrBr
Br
(more stablebenzylic radical)
(less stable)
Br+ H Br
Br
Ch. 15 - 101
Mechanism (bottom reaction):
H Br
H
H
(more stablebenzylic cation)
(less stable)
Br
Br
Ch. 15 - 102
13C. 13C. Oxidation of the Side ChainOxidation of the Side Chain
CH3OH
O
1. KMnO4, OH-,
2. H3O+
(100%)
Ch. 15 - 103
OH
O
1. KMnO4, OH-,
2. H3O+
OH
O
1. KMnO4, OH-,
2. H3O+
OH
O
1. KMnO4, OH-,
2. H3O+
OH
O
1. KMnO4, OH-,
2. H3O+
O
Ch. 15 - 104
Using hot alkaline KMnO4, alkyl, alkenyl, alkynyl and acyl groups all oxidized to –COOH group.
For alkyl benzene, 3o alkyl groups resist oxidation.
1. KMnO4, OH-,
2. H3O+
No Reaction
●Need benzylic hydrogen for alkyl group oxidation.
Ch. 15 - 105
13D. 13D. Oxidation of the Benzene RingOxidation of the Benzene Ring
R1. O3, CH3CO2H
2. H2O2
R
OH
O
Ch. 15 - 106
14.Synthetic Applications
CH3
NO2
How?
Ch. 15 - 107
CH3
NO2
CH3
CH3Cl
AlCl3
conc. HNO3
conc. H2SO4heat
CH3
NO2
+
CH3 group: ortho-, para-directing. NO2 group: meta-directing.
Ch. 15 - 108
NO2
CH3Cl
AlCl3
conc. HNO3
conc. H2SO4heat
CH3
NO2
CH3
NO2
NOT
If the order is reversed the wrong regioisomer is given.
This gives very poor yields anyway.
F.C. is not effective on a deactivated ring.
Ch. 15 - 109
We do not know how to substitute a hydrogen on a benzene ring with a –COOH group. However, side chain oxidation of alkylbenzene could provide the –COOH group.
Both the –COOH group and the NO2 group are meta-directing.
COOH
NO2
Ch. 15 - 110
CH3Cl
AlCl3
conc. HNO3
conc. H2SO4heat
COOH
NO2
CH3
NO2
NO2
1. KMnO4, OH-,
2. H3O+
Route 1:
(Poor yield)
Ch. 15 - 111
CH3Cl
AlCl3
conc. HNO3
conc. H2SO4heat
COOH
COOH
NO2
1. KMnO4, OH-,
2. H3O+
CH3
Route 2:
(Better method)
Ch. 15 - 112
Which synthetic route is better?●Recall “Limitations of Friedel-
Crafts Reactions, Section 15.8” Friedel–Crafts reactions usually
give poor yields when powerful electron-withdrawing groups are present on the aromatic ring or when the ring bears an –NH2, –NHR, or –NR2 group. This applies to both alkylations and acylations.
Route 2 is a better route.
Ch. 15 - 113
Both Br and Et groups are ortho-, para-directing.
How to make them meta to each other ?
Recall: an acyl group is meta-directing and can be reduced to an alkyl group by Clemmensen ketone reduction.
Br
Ch. 15 - 114
Br
O
Cl
AlCl3
O
O
Br
Br2FeBr3
Zn/Hg
HCl, heat
Ch. 15 - 115
14A. 14A. Use of Protecting and BlockingUse of Protecting and Blocking GroupsGroups
NH2 NH2?
Br
Protected amino groups.●Example:
Ch. 15 - 116
NH2 NH2
Br
Br2NH2
Br
NH2
Br Br
Br
+ others
+
+
Problem Not a selective synthesis, o- and
p-products + dibromo and tribromo products.
Ch. 15 - 117
NH2 CH3 Cl
O
N O
CH3
H
pyridine
(an amide)
Solution Introduction of a deactivated
group on –NH2.
Ch. 15 - 118
The amide group is less activating than –NH2 group. ●No problem for over
bromination.
The steric bulkiness of this group also decreases the formation of o-product.
Ch. 15 - 119
NH2 NH2
Br
NHCOCH3 NHCOCH3
Br
Cl
OH2SO4,
H2O,
OH-
Br2, FeBr3
pyridine
(hydrolysisof amide)
1.
2.
Ch. 15 - 120
NH2 NH2
Br
Problem Difficult to get o-product without
getting p-product. Due to excessive bromination.
Ch. 15 - 121
NH2 NH2
NO2
Cl
O
NHCOCH3 NHCOCH3
HO3S
NHCOCH3
HO3S NO2
pyridine
SO3 conc. H2SO4
60oC
HNO3H2SO4
1.
2.
dil. H2SO4
100oC
OH-
Solution Use of a –SO3H blocking group at
the p-position which can be removed later.
Ch. 15 - 122
14B. 14B. Orientation in DisubstitutedOrientation in Disubstituted BenzenesBenzenes
Directing effect of EDG usually outweighs that of EWG.
With two EDGs, the directing effect is usually controlled by the stronger EDG.
Ch. 15 - 123
NO2
CH3
CF3
CH3
CF3
NO2
(i)
Examples (only major product(s) shown):
OMe
COCH3
OMe
COCH3
OMe
COCH3
Br
Br
Br
(ii) +
Ch. 15 - 124
Substitution does not occur to an appreciable extent between meta- substituents if another position is open.
Cl
Br
Cl
Br
Cl
Br
HNO3
H2SO4+
NO2
O2N
62% 37%
XCl
Br
+
NO2
1%
Ch. 15 - 125
NO2
NHCOCH3 NHCOCH3
NHCOCH3
COOMe COOMe
COOMe
O2N
NO2
(iii)
+
Ch. 15 - 126
OCH3
CH3
OCH3
CH3
OCH3
CH3
Cl
Cl
Cl
(iv)
+
Ch. 15 - 127
Cl
Cl Cl
Br
Br
Br
NO2NO2
NO2
(v)
+
Ch. 15 - 128
15. Allylic and Benzylic Halides inNucleophilic Substitution Reactions
C C
CH2X
C C
C
R
X
H
C C
C
R'
X
R
1o Allylic 2o Allylic 3o Allylic
1o Benzylic 2o Benzylic 3o Benzylic
CAr
R
H
X CAr
R'
R
XCAr
H
H
X
Ch. 15 - 129
H3C X R CH2 X R CH X
R'
A Summary of Alkyl, Allylic, & Benzylic Halides in SN Reactions:
●These halides give mainly SN2 reactions.
●These halides may give either SN1 or SN2 reactions.
Ar CH2 X Ar CH X
R
C C
CH2 X
C C
C
R
X
H
Ch. 15 - 130
A Summary of Alkyl, Allylic, & Benzylic Halides in SN Reactions:
●These halides give mainly SN1 reactions.
C C
C
R'
X
R
C XR'
R
R"
C XAr
R
R'
Ch. 15 - 131
16.Reduction of AromaticCompounds
H2/Ni
slow
H2/Ni
fast
H2/Nifast
+
benzene cyclohexadienes cyclohexene
cyclohexane
Ch. 15 - 132
16A. 16A. The Birch ReductionThe Birch Reduction
benzene
Na
NH3, EtOH
1,4-cyclohexadiene
Ch. 15 - 133
Mechanism:
benzene
Na
benzene radical anion
etc.
EtOH
cyclohexadienyl radical
etc.
H
H
H
HNa
cyclohexadienyl anion
etc.
H
H
H
H
H
H
H
H
1,4-cyclohexadiene
EtOH
Ch. 15 - 134
Synthesis of 2-cyclohexenones:
OCH3Li
liq. NH3EtOH
OCH3
O
2-cyclohexenone
H3O+
H2O
(84%)
Ch. 15 - 135
END OF CHAPTER 15