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