Created byProfessor William Tam & Dr. Phillis

Chang Ch. 15 - 1

..Reactions ofReactions of

Aromatic CompoundsAromatic Compounds

Based on Solomons , FryhleBased on Solomons , Fryhle

Organic Chemistry 10Organic Chemistry 10thth. Edition. Edition

Ch. 15- 2

About The AuthorsAbout The Authors

These PowerPoint Lecture Slides were created and prepared by Professor William Tam and his wife, Dr. Phillis Chang.

Professor William Tam received his B.Sc. at the University of Hong Kong in 1990 and his Ph.D. at the University of Toronto (Canada) in 1995. He was an NSERC postdoctoral fellow at the Imperial College (UK) and at Harvard University (USA). He joined the Department of Chemistry at the University of Guelph (Ontario, Canada) in 1998 and is currently a Full Professor and Associate Chair in the department. Professor Tam has received several awards in research and teaching, and according to Essential Science Indicators, he is currently ranked as the Top 1% most cited Chemists worldwide. He has published four books and over 80 scientific papers in top international journals such as J. Am. Chem. Soc., Angew. Chem., Org. Lett., and J. Org. Chem.

Dr. Phillis Chang received her B.Sc. at New York University (USA) in 1994, her M.Sc. and Ph.D. in 1997 and 2001 at the University of Guelph (Canada). She lives in Guelph with her husband, William, and their son, Matthew.

Ch. 15 - 3

1. Electrophilic AromaticSubstitution Reactions

Overall reaction

H E

H+E++

Ch. 15 - 4

X

X2

FeX3

NO2

HNO3

H2SO4

R

RClAlCl3

R

O R Cl

O

AlCl3

SO3H

H2SO4

SO3

Ch. 15 - 5

2. A General Mechanism for Electro-philic Aromatic Substitution

Different chemistry with alkene

C

CBr2

Br C

C Br

Br2

+

+ No Reaction

Ch. 15 - 6

Benzene does not undergo electrophilic addition, but it undergoes electrophilic aromatic substitution

+

HE A

H A

E

(H substituted by E)

Ch. 15 - 7

Mechanism●Step 1

E+ E

slowr.d.s.

E

E

Ch. 15 - 8

E

H

B

Mechanism●Step 2

E

B H+fast

Ch. 15 - 9

Ch. 15 - 10

3. Halogenation of Benzene

Benzene does not react with Br2 or Cl2 unless a Lewis acid is present (catalytic amount is usually enough)

Ch. 15 - 11

ExamplesCl

HClCl2

+FeCl325o

(90%)

Br

HBrBr2

+FeCl3heat

(75%)

●Reactivity: F2 > Cl2 > Br2 > I2

Ch. 15 - 12

Mechanism

Br Br

FeBr3

(weakelectrophile)

Br Br FeBr3

Br + FeBr4

(very reactiveelectrophile)

Ch. 15 - 13

BrBrBr

Brslow r.d.s.

Mechanism (Cont’d)

Ch. 15 - 14

Mechanism (Cont’d)

Br

HBr FeBr3 Br

Br H+

+ FeBr3

Ch. 15 - 15

F2: too reactive, give mixture of mono-, di- and highly substituted products

F F F

F

F

+ +

+ others

F2Lewisacid

Ch. 15 - 16

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 - 17

4. Nitration of Benzene

Electrophile in this case is NO2

(nitronium ion)

conc. HNO3NO2

+ H3O+

+ HSO4

conc. H2SO4

50-60oC (85%)

Ch. 15 - 18

Mechanism

O

S

O

OHO H N

O

O

HO+

HSO4 N

O

O

O

H

H

+ N OO H2O

(NO2)

+

Ch. 15 - 19

NO2slow r.d.s.

NO2NO2NO2

Mechanism (Cont’d)

Ch. 15 - 20

Mechanism (Cont’d)

NO2

HH2O NO2

+ H3O+

Ch. 15 - 21

5. Sulfonation of Benzene Mechanism

●Step 1+ +2 H2SO4 SO3 H3O

+ HSO4

●Step 2O

SO O

H

SO

O

O

slow

otherresonancestructures

Ch. 15 - 22

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 - 23

SO3H

SO3, conc. H2SO4

25oC - 80oC

Sulfonation & Desulfonation

dil. H2SO4

H2O, 100oC

Ch. 15 - 24

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 - 25

Mechanism

Cl AlCl3 Cl AlCl3

AlCl4+

Ch. 15 - 26

Mechanism (Cont’d)

Ch. 15 - 27

Mechanism (Cont’d)

HCl AlCl3

+ HCl

+ AlCl3

Ch. 15 - 28

Note: Not necessary to start with alkyl halide, other possible functional groups can be used to generate a reactive carbocation

+ H+

e.g.

H+via

Ch. 15 - 29

OH

BF3

60oC+

O BF3

Hvia

Ch. 15 - 30

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 - 31

Mechanism

O

R ClAlCl3+

R C O R C O

O

CR Cl AlCl3

Ch. 15 - 32

Mechanism (Cont’d)

R C O

R

O

R

O

R

O

Ch. 15 - 33

Mechanism (Cont’d)

H

O

RCl AlCl3

+ HCl

+ AlCl3

R

O

Ch. 15 - 34

Acid chlorides (or acyl chlorides)

RC

O

Cl

RC

O

OH RC

O

Clor

SOCl2

PCl5

●Can be prepared by

Ch. 15 - 35

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 - 36

(How is thisFormed?)

(not formed) For example

AlCl3Cl+

AlCl3

Ch. 15 - 37

1o cation (not stable)

Reason

Cl AlCl3

HAlCl4+ +

1,2-hydride shift

H 3o cation(more stable)

Ch. 15 - 38

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

NO2

>

N(CH3)3

> > >

CF3

>

SO3H

>

NH2O OH O R

These usually give poor yields in Friedel-Crafts

reactions

Ch. 15 - 39

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 - 40

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 - 41

Polyalkylations often occur

+OH

+BF3

60oC

(24%) (14%)

Ch. 15 - 42

9. Synthetic Applications ofFriedel-Crafts Acylations: The Clemmensen Reduction

Clemmensen ketone reduction

HClreflux

R

O

RZn/Hg

Ch. 15 - 43

Clemmensen ketone reduction●A very useful reaction for

making alkyl benzene that cannot be made via Friedel-Crafts alkylations

?

e.g.

Ch. 15 - 44

Clemmensen ketone reduction●Cannot use Friedel-Crafts

alkylation

Cl

AlCl3

give

butNOT

Ch. 15 - 45

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 - 46

Cl

AlCl3

OO Zn/Hg

conc. HClreflux

Ch. 15 - 47

10.Substituents Can Affect Boththe Reactivity of the Ring and the Orientation of the Incoming Group

Two questions we would like to address here●Reactivity●Regiochemistry

Ch. 15 - 48

●ReactivityY Y

E

E

faster or slower than E

E

Y = EDG (electron-donating group) or EWG (electron-withdrawing group)

Ch. 15 - 49

●RegiochemistryY

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 - 50

G

E A+

GE

Hotherresonancestructure

A substituted

benzene

Electrophilic reagent Areniu

m ion

Ch. 15 - 51

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 - 52

●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 - 53

●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 - 54

Y

EDG

–H

EWGIncr

easi

ng a

ctiv

ity

●Reactivity

Ch. 15 - 55

●Reactivity

EDG (electron-donating group) on benzene ring Increases electron

density in the benzene ring

More reactive towards electrophilic aromatic substitution

Ch. 15 - 56

●Reactivity

EWG (electron-withdrawing group) on benzene ring Decreases electron

density in the benzene ring

Less reactive towards electrophilic aromatic substitution

Ch. 15 - 57

●Reactivity towards electrophilic aromatic substitution

EDG EWG

> >

Ch. 15 - 58

Regiochemistry: directing effect

●General aspects Either o-, p- directing or m-

directing Rate-determining-step is -

electrons on the benzene ring attacking an electrophile (E)

Ch. 15 - 59

orthoattack

YYY

o-I o-II o-III

EEE

Y

E

Ch. 15 - 60

metaattack

YYY

m-I m-II m-IIIE E E

Y

E

Ch. 15 - 61

paraattack

p-I p-II p-III

YYY

E E E

Y

E

Ch. 15 - 62

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 - 63

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 - 64

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 - 65

Classification of different substituentsY

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 - 66

Classification of different substituentsY

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 - 67

11.How Substituents AffectElectrophilic AromaticSubstitution: A Closer Look

Ch. 15 - 68

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 - 69

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 - 70

Ch. 15 - 71

Two types of EDG(i)

11B. 11B. Inductive and Resonance Effects:Inductive and Resonance Effects: Theory of OrientationTheory of Orientation

by positive mesomeric effect (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 - 72

Two types of EDG

●Positive mesomeric 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 - 73

Similar to EDG, EWG can withdraw electrons from the benzene ring by resonance effect (negative mesomeric 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 - 74

EWG = –COOR, –COR, –CHO, –CF3, –NO2, etc.

11C. 11C. Meta-Directing GroupsMeta-Directing Groups

EWG EWG

E

E

(major)

(EWG ≠ halogen)

Ch. 15 - 75

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 - 76

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 - 77

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 - 78

EDG = –NR2, –OR, –OH, etc.

11D. 11D. OrthoOrtho––Para-Directing GroupsPara-Directing Groups

EDG EDG

E

(major)

E

EDG

E

+

ortho para

Ch. 15 - 79

OCH3

OCH3

NO2

OCH3

NO2

OCH3

NO2

OCH3

NO2

OCH3

NO2

NO2

(ortho)

- H+

(ortho)(favorable)

For example

(extra resonance structure due to positive mesomeric effect of –OCH3)

Ch. 15 - 80

OCH3 OCH3OCH3

OCH3

OCH3

(para)

NO2 NO2NO2

NO2

- H+

OCH3

NO2

(para)(favorable)

NO2

(extra resonance structure due to positive mesomeric effect of –OCH3)

Ch. 15 - 81

OCH3 OCH3OCH3

OCH3

NO2

(meta)

- H+

OCH3

NO2 NO2 NO2

NO2

(meta)(less favorable)

(3 resonance structures only, no extra stabilization by positive mesomeric effect of –OCH3) less favorable

Ch. 15 - 82

For halogens, two opposing effects

negative inductive effect withdrawing

electron density from the

benzene ring

ClCl

>

positive mesomeric effect donating

electrondensity to thebenzene ring

Ch. 15 - 83

Overall●Halogens are weak

deactivating groups Negative inductive effect >

positive mesomeric effect in this case)

Ch. 15 - 84

Cl

Cl

NO2

Cl

NO2

Cl

NO2

Cl

NO2

Cl

NO2

NO2

(ortho)

- H+

(ortho)(favorable)

Regiochemistry

(extra resonance structure due to positive mesomeric effect of –Cl)

Ch. 15 - 85

Cl ClCl

Cl

Cl

(para)

NO2 NO2NO2

NO2

- H+

Cl

NO2

(para)(favorable)

NO2

(extra resonance structure due to positive mesomeric effect of –Cl)

Ch. 15 - 86

Cl ClCl

Cl

NO2

(meta)

- H+

Cl

NO2 NO2 NO2

NO2

(meta)(less favorable)

(3 resonance structures only, no extra stabilization by positive mesomeric effect of –Cl) less favorable

Ch. 15 - 87

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 - 88

CH3

E

CH3

E

CH3

E

CH3

E

>

Ortho attack

Relatively stable contributor

Ch. 15 - 89

CH3

E

CH3 CH3 CH3

EEE

Meta attack

Ch. 15 - 90

CH3

E

CH3 CH3 CH3

E E E

>

Para attack

Relatively stable contributor

Ch. 15 - 91

12.Reactions of the Side Chainof Alkylbenzenes

CH3

Methylbenzene(toluene)

Ethylbenzene Isopropylbenzene(cumene)

Phenylethene(styrene or

vinylbenzene)

Ch. 15 - 92

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 - 93

C

- LG

C

A benzylcation

LG

CC C C

Benzylic cations are stabilized by resonance

Ch. 15 - 94

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 - 95

Mechanism●Chain initiation

2 XX Xperoxides

heat orlight

●Chain propagation

X

H

CC6H5 H

H

+

H

CC6H5

H

H X+

Ch. 15 - 96

●Chain propagation

●Chain termination

X

H

CC6H5 X

H

+

H

CC6H5

H

+X X

X

H

CC6H5 X

H

+

H

CC6H5

H

Ch. 15 - 97

e.g.

NBS

h

(more stable benzylic radicals)

(less stable 1o radicals)

Br

+

Br

(major) (very little)

Ch. 15 - 98

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 - 99

Example

H+

heatOH

(not observed)

Ha Hb

- Ha

- Hb

Ch. 15 - 100

13B. 13B. Additions to the Double Bond ofAdditions to the Double Bond of AlkenylbenzenesAlkenylbenzenes

HBr

RO ORheat

HBr

(noperoxides)

Br

Br

Ch. 15 - 101

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 - 102

Mechanism (bottom reaction)

H Br

H

H

(more stablebenzylic cation)

(less stable)

Br

Br

Ch. 15 - 103

13C. 13C. Oxidation of the Side ChainOxidation of the Side Chain

CH3OH

O

1. KMnO4, OH-,

2. H3O+

(100%)

Ch. 15 - 104

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 - 105

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 - 106

13D. 13D. Oxidation of the Benzene RingOxidation of the Benzene Ring

R1. O3, CH3CO2H

2. H2O2

R

OH

O

Ch. 15 - 107

14.Synthetic Applications

CH3

NO2

How?

Ch. 15 - 108

CH3

NO2

CH3

CH3Cl

AlCl3

conc. HNO3

conc. H2SO4heat

CH3

NO2

+

CH3 group: ortho-, para-directing NO2 group: meta-directing

Ch. 15 - 109

NO2

CH3Cl

AlCl3

conc. HNO3

conc. H2SO4heat

CH3

NO2

CH3

NO2

NOT

If the order is reversed the wrong regioisomer is given

Ch. 15 - 110

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 - 111

CH3Cl

AlCl3

conc. HNO3

conc. H2SO4heat

COOH

NO2

CH3

NO2

NO2

1. KMnO4, OH-,

2. H3O+

Route 1

Ch. 15 - 112

CH3Cl

AlCl3

conc. HNO3

conc. H2SO4heat

COOH

COOH

NO2

1. KMnO4, OH-,

2. H3O+

CH3

Route 2

Ch. 15 - 113

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 - 114

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 - 115

Br

O

Cl

AlCl3

O

O

Br

Br2FeBr3

Zn/Hg

HCl, heat

Ch. 15 - 116

14A. 14A. Use of Protecting and BlockingUse of Protecting and Blocking GroupsGroups

NH2 NH2?

Br

Protected amino groups●Example

Ch. 15 - 117

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 - 118

NH2 CH3 Cl

O

N O

CH3

H

pyridine

(an amide)

Solution Introduction of a deactivated

group on –NH2

Ch. 15 - 119

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 - 120

NH2 NH2

Br

NHCOCH3 NHCOCH3

Br

Cl

OH2SO4,

H2O,

OH-

Br2, FeBr3

pyridine

(hydrolysisof amide)

1.

2.

Ch. 15 - 121

NH2 NH2

Br

Problem Difficult to get o-product without

getting p-product Over nitration

Ch. 15 - 122

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 - 123

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 - 124

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 - 125

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 - 126

NO2

NHCOCH3 NHCOCH3

NHCOCH3

COOMe COOMe

COOMe

O2N

NO2

(iii)

+

Ch. 15 - 127

OCH3

CH3

OCH3

CH3

OCH3

CH3

Cl

Cl

Cl

(iv)

+

Ch. 15 - 128

Cl

Cl Cl

Br

Br

Br

NO2NO2

NO2

(v)

+

Ch. 15 - 129

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 - 130

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 - 131

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 - 132

16.Reduction of AromaticCompounds

H2/Ni

slow

H2/Ni

fast

H2/Nifast

+

benzene cyclohexadienes cyclohexene

cyclohexane

Ch. 15 - 133

16A. 16A. The Birch ReductionThe Birch Reduction

benzene

Na

NH3, EtOH

1,4-cyclohexadiene

Ch. 15 - 134

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 - 135

Synthesis of 2-cyclohexenones

OCH3Li

liq. NH3EtOH

OCH3

O

2-cyclohexenone

H3O+

H2O

(84%)

Ch. 15 - 136

END OF CHAPTER 15