Electrophillic Aromatci Substitution

7/28/2019 Electrophillic Aromatci Substitution

1/114

1

Treatment of cyclooctatetrene with potassium gives you a

dianion. Classify the starting material and product as

aromatic, antiaromatic or nonaromatic?

2 K


2/114

2


3/114

3

Classify cyclononatetrene and its various ions as

either aromatic, antiaromatic or nonaromatic.


4/114

4


5/114

5

Electrophilic Aromatic Substitution

The characteristic reaction of benzene is electrophilic aromaticsubstitutiona hydrogen atom is replaced by an electrophile.

Background


6/114

6

Benzene does not undergo addition reactions like other

unsaturated hydrocarbons, because addition would yield

a product that is not aromatic.

Substitution of a hydrogen keeps the aromatic ring

intact.

There are five main examples of electrophilic aromatic

substitution.


7/114

7


8/114

8

Regardless of the electrophile used, all electrophilic aromatic

substitution reactions occur by the same two-step mechanism

addition of the electrophile E+ to form a resonance-stabilized

carbocation, followed by deprotonation with base, as shownbelow:


9/114

9

The first step in electrophilic aromatic substitution forms a

carbocation, for which three resonance structures can be

drawn. To help keep track of the location of the positive

charge:


10/114

10

The energy changes in electrophilic aromatic substitution are

shown below:


11/114

11

In halogenation, benzene reacts with Cl2 or Br2 in the

presence of a Lewis acid catalyst, such as FeCl3 or

FeBr3, to give the aryl halides chlorobenzene or

bromobenzene respectively.

Analogous reactions with I2 and F2 are not synthetically

useful because I2 is too unreactive and F2 reacts tooviolently.

Halogenation


12/114

12

Chlorination proceeds by a similar mechanism.


13/114

13

Nitration and sulfonation introduce two different functional

groups into the aromatic ring.

Nitration is especially useful because the nitro group can be

reduced to an NH2 group.

Nitration and Sulfonation


14/114

14

Generation of the electrophile in nitration requires

strong acid.


15/114

15

Generation of the electrophile in sulfonation requires

strong acid.


16/114

16

In Friedel-Crafts alkylation, treatment of benzene with an

alkyl halide and a Lewis acid (AlCl3) forms an alkyl

benzene.

Friedel-Crafts Alkylation and Friedel-Crafts Acylation


17/114

17

In Friedel-Crafts acylation, a benzene ring is treated with

an acid chloride (RCOCl) and AlCl3 to form a ketone.

Because the new group bonded to the benzene ring is

called an acyl group, the transfer of an acyl group from

one atom to another is an acylation.


18/114

18

Friedel-Crafts Alkylation and Friedel-Crafts Acylation


19/114

19


20/114

20

In Friedel-Crafts acylation, the Lewis acid AlCl3 ionizes the

carbon-halogen bond of the acid chloride, thus forming a

positively charged carbon electrophile called an acylium ion,which is resonance stabilized.

The positively charged carbon atom of the acylium ion then goes

on to react with benzene in the two step mechanism of

electrophilic aromatic substitution.


21/114

21

Three additional facts about Friedel-Crafts alkylation

should be kept in mind.

[1] Vinyl halides and aryl halides do not react in Friedel-

Crafts alkylation.


22/114

22

[2] Rearrangements can occur.

These results can be explained by carbocation

rearrangements.


23/114

23


24/114

24

Rearrangements can occur even when no free carbocation

is formed initially.


25/114

25

[3] Other functional groups that form carbocations can

also be used as starting materials.


26/114

26

Each carbocation can then go on to react with benzene to

form a product of electrophilic aromatic substitution. For

example:


27/114

27

Starting materials that contain both a benzene ring and an

electrophile are capable of intramolecular Friedel-Crafts

reactions.


28/114

28

For Monday, do problems 18.1-18.11.


29/114

29

1) Why is benzene less reactive than an alkene?

The pi electrons of benzene are delocalized over 6atoms, thus making benzene more stable and less

available for electron donation.

While an alkenes electrons are localized between two

atoms, thus making it more nucleophillc and morereactive toward electrophiles.


30/114

30

2) Show how the other two resonance structures can be

deprotonated in step two of electrophillic aromatic

substitution.H

E

B

E

H

E

BE


31/114

31

H

E

B

E


32/114

32

3) Draw a detailed mechanism of the chlorination of

benzene.

Cl ClFeCl3 Cl Cl FeCl3

Formation of Electrophile

Cl Cl FeCl3

HH

Cl

H

Cl

H

Cl

+ FeCl4

Electrophillic Additon


33/114

33

H

Cl

FeCl4

Cl

+ HCl + FeCl3

Deprotonation


34/114

34

4) Draw stepwise mechanism for the sulfonation of A.

SO3

H2SO4

SO3H

a

b

O

S

O O

H OSO3H SO3H+ HSO4



35/114

35

H

SO3H

RR

H

SO3H

R

H

SO3H

R

H

SO3H

Electrophillic Addition

R

H

SO3H

HSO4R

SO3H

+ H2SO4

Deprotonation


36/114

36

5) What product is formed when benzene is reacted with

each of the following alkyl halides?

+ (CH3)2CHClAlCl3

a)CH(CH3)2

+

Cl

AlCl3

b)


37/114

37

+

AlCl3H3CH2C

Cl

O

c) O

CH2CH3


38/114

38

6) What acid chloride is necessary to produce each

product from benzene using a Friedal-Crafts acylation?

O

CH2CH2CH(CH3)2

a)

Cl

O

CH2CH2CH(CH3)2

O

b)O

Cl


39/114

39

O

c)

O

Cl


40/114

40

7) Draw a stepwise mechanism for the following

friedal-Crafts alkylation?

+ CH3CH2Cl

AlCl3

CH2CH3

CH3CH2Cl AlCl3H3CH2C Cl AlCl3



41/114

41

H3CH2C Cl AlCl3

HH

CH2CH3

H

CH2CH3

H

CH2CH3

Electrophillic Additoon

H

CH2CH3

AlCl3Cl

CH2CH3

+ HCl + AlCl3

Protonation


42/114

42

8) Which of these halides are reactive in a Friedal-Crafts

alkylation?

Br

A

Br

B

Br

CBr

D

Br

B

Br

D

Look at the carbon to which the halogen is

attached and determine its hybridization. If sp2 its

unreactive, while sp3 is reactive.


43/114

43

9) Draw a stepwise mechanism for the following

reaction.

+ (CHe)2CHCH2ClAlCl3

C(CH3)3

+ HCl + AlCl3

H3C

CH3

H

H2C Cl

AlCl3H3C

CH3

H

H2C Cl AlCl3

H3C

CH3

CH3+ AlCl4


1,2 H shift



44/114

44

H3C

CH3

CH3

H H C(CH3)3 H C(CH3)3 H C(CH3)3


H C(CH3)3

AlCl4

C(CH3)3

+ AlCl3 + HCl

Deprotonation

10) Draw the product of each reaction


45/114

45

10) Draw the product of each reaction

+H2SO4

a)

+

H2SO4

(H3C)2C CH2

b)

C(CH3)3

)


46/114

46

+H

2SO

4

OH

c)

+H2SO4

OHd)


47/114

47

11) Draw a stepwise mechanism for the intermolecular

Friedal-Crafts acylation below

Cl

Cl

OCl

AlCl3

Cl

Cl

O

+ HCl + AlCl3



48/114

48

Cl

Cl

OCl

AlCl3

Cl

Cl

OClCl3Al

Cl

Cl

O

Cl

Cl

O

+ AlCl4


Electrophillic addition


49/114

49

Cl

Cl

O

Cl

Cl

O

H

Cl

Cl

O

H

Cl

Cl

O

H

Electrophillic addition

Deprotonation


50/114

50

Cl

Cl

O

HAlCl4

Cl

Cl

O

+ HCl + AlCl3

Deprotonation


51/114

51

Substituted Benzenes

Many substituted benzene rings undergo electrophilic

aromatic substitution.

Each substituent either increases or decreases the

electron density in the benzene ring, and this affects the

course of electrophilic aromatic substitution.


52/114

52

Considering inductive effects only, the NH2 group

withdraws electron density and CH3 donates electron

density.


53/114

53

Resonance effects are only observed with substituents

containing lone pairs or bonds.

An electron-donating resonance effect is observed

whenever an atom Z having a lone pair of electrons is

directly bonded to a benzene ring.


54/114

54

An electron-withdrawing resonance effect is observed in

substituted benzenes having the general structure

C6H5-Y=Z, where Z is more electronegative than Y.

Seven resonance structures can be drawn for

benzaldehyde (C6H5CHO). Because three of them place a

positive charge on a carbon atom of the benzene ring,

the CHO group withdraws electrons from the benzenering by a resonance effect.


55/114

55

To predict whether a substituted benzene is more or less

electron rich than benzene itself, we must consider the

net balance of both the inductive and resonance effects.

For example, alkyl groups donate electrons by an

inductive effect, but they have no resonance effect

because they lack nonbonded electron pairs or bonds.

Thus, any alkyl-substituted benzene is more electron

rich than benzene itself.


56/114

56

The inductive and resonance effects in compounds having thegeneral structure C6H5-Y=Z (with Z more electronegative than Y)

are both electron withdrawing.


57/114

57

These compounds represent examples of the general

structural features in electron-donating and electron

withdrawing substituents.


58/114

58

Electrophilic Aromatic Substitution and Substituted

Benzenes.

Electrophilic aromatic substitution is a general reactionof all aromatic compounds, including polycyclic

aromatic hydrocarbons, heterocycles, and substituted

benzene derivatives.

A substituent affects two aspects of the electrophilicaromatic substitution reaction:

1. The rate of the reactionA substituted benzene

reacts faster or slower than benzene itself.

2. The orientationThe new group is located either

ortho, meta, or para to the existing substituent.

The identity of the first substituent determines the

position of the second incoming substituent.


59/114

59

Consider tolueneToluene reacts faster than benzene

in all substitution reactions.

The electron-donating CH3 group activates the benzenering to electrophilic attack.

Ortho and para products predominate.

The CH3 group is called an ortho, para director.


60/114

60

Consider nitrobenzeneIt reacts more slowly than

benzene in all substitution reactions.

The electron-withdrawing NO2 group deactivates thebenzene ring to electrophilic attack.

The meta product predominates.

The NO2 group is called a meta director.


61/114

61

All substituents can be divided into three general types:


62/114

62


63/114

63

Keep in mind that halogens are in a class by

themselves.

Also note that:


64/114

64

To understand how substituents activate or deactivate the ring,

we must consider the first step in electrophilic aromatic

substitution.

The first step involves addition of the electrophile (E+) to form aresonance stabilized carbocation.

The Hammond postulate makes it possible to predict the relative

rate of the reaction by looking at the stability of the carbocation

intermediate.


65/114

65

The principles of inductive effects and resonance effects can

now be used to predict carbocation stability.


66/114

66

The energy diagrams below illustrate the effect of electron-

withdrawing and electron-donating groups on the transition state

energy of the rate-determining step.

Figure 18.6 Energy diagrams comparing the rate of electrophilic substitution of substituted benzenes


67/114

67

O i t ti Eff t i S b tit t d B


68/114

68

Orientation Effects in Substituted Benzenes

There are two general types of ortho, para directors and

one general type of meta director. All ortho, para directors are R groups or have a

nonbonded electron pair on the atom bonded to the

benzene ring.

All meta directors have a full or partial positive chargeon the atom bonded to the benzene ring.


69/114

69

To evaluate the effects of a given substituent, we can use

the following stepwise procedure:


70/114

70

A CH3 group directs electrophilic attack ortho and para to itself

because an electron-donating inductive effect stabilizes the

carbocation intermediate.


71/114

71

An NH2 group directs electrophilic attack ortho and para to itself

because the carbocation intermediate has additional resonance

stabilization.

With the NO group (and all meta directors) meta attack occurs


72/114

72

With the NO2 group (and all meta directors) meta attack occurs

because attack at the ortho and para position gives a

destabilized carbocation intermediate.


73/114

73

Figure 18.7The reactivity and directing

effects of common substituted

benezenes

F W d d


74/114

74

For Wednesday:

Draw out stepwise mechanisms for 10b and c.

18.12-18.20 as well.

10b)


75/114

)

(H3C)2C CH2 H O SO3H (H3C)2C CH3HSO4

+H2SO4

(H3C)2C CH2

C(CH3)3




76/114

C(CH3)3

C(CH3)3 C(CH3)3

C(CH3)3

H

H H

H

C(CH3)3

H HSO4

C(CH3)3

+ H2S04

Deprotonation

10c)


77/114

+H2SO4

OH

OH H O SO3HOH2

+ HSO4

+ H2O + HSO4




78/114

HH

H

H

Deprotonation


79/114

H

HSO4

12)Identify each group as having an electron


80/114

) y g p g

donating or electron withdrawing inductive effect.

a) CH3CH2CH2CH2-

Electron donating

b) Br-

Electron withdrawing

c) CH3CH2O-

Electron withdrawing

13) Draw the resonance structures and use them to


81/114

determine whether there is an electron donating or

withdrawing resonance effect.

OCH3 OCH3 OCH3OCH3

OCH3

OCH3

a)

Negative charge on ring, electron donating effect

b)O


82/114

O OO

O

OO

O

Positive charge, electron

withdrawing

14)Identify as electron donating or electron withdrawing


83/114

14)Identify as electron donating or electron withdrawing.

a)OCH3

Lone pair on oxygen, electron

donating

b) I Halogen, electronwithdrawing

c) C(CH3)3 Alkyl group, electron

donating

15)Predict the products.


84/114

OCH3

CH3CH2Cl

AlCl3

a)OCH3

CH2CH3

+

OCH3

H3CH2C

b) Br HNO3H2SO4

Br

NO2

+

Br

O2N

c)


85/114

NO2

Cl2

FeCl3

NO2

Cl

16)Predict the products when reacted with HNO3 and

H2SO4 Also state whether the reactant is more or less


86/114

H2SO4. Also state whether the reactant is more or less

reactive than benzene.

a)O

O

NO2

N

b)N

O2N

Less

Less

c) OHOH OH


87/114

Cl Cl

NO2

+

Cl

O2N

Less

d)

NO2

+

O2N

More

CH2CH3

d)


88/114

CH2CH3CH2CH3

NO2

+

CH2CH3

O2N

More

17)Label each compound as less or more reactive


89/114

than benzene.

a)

C(CH3)3

more

OH

OH

b)

more

c)O


90/114

O

OCH2CH3 less

N(CH3)3

d)

less

18) Rank each group in order of increasing reactivity.


91/114

Cl OCH3

a)

2 3 1

NO2 CH3

b)

2 3 1

19) Draw the resonance structures of ortho attack by NO2.


92/114

Label any resonance structure that is especially stable or

unstable.

C(CH3)3a)

C(CH3)3

NO2

C(CH3)3

NO2

C(CH3)3

NO2

C(CH3)3

NO2

Most stable


93/114

c) O


94/114

O

NO2

O

NO2

O

NO2

O

NO2

O

NO2

Vey

unstable

20) Show why chlorine is an ortho para director.


95/114

Cl

E

Cl

E

Cl

E

Cl

E

Cl

E

Especially stable, every atom has an octet

Cl


96/114

Cl

E

Cl

E

Cl

E

Cl

E

Cl

Cl Cl


97/114

E

E E

Cl

E

Especially stable, every

atom has an octet

Limitations in Electrophilic Aromatic Substitutions


98/114

98

Benzene rings activated by strong electron-donating groups

OH, NH2, and their derivatives (OR, NHR, and NR2)undergopolyhalogenation when treated with X2 and FeX3.

A benzene ring deactivated by strong electron-withdrawing


99/114

99

A benzene ring deactivated by strong electron-withdrawing

groups (i.e., any of the meta directors) is not electron rich

enough to undergo Friedel-Crafts reactions.

Friedel-Crafts reactions also do not occur with NH2 groups

because the complex that forms between the NH2 group and the

AlCl3 catalyst deactivates the ring towards Friedel-Crafts

reactions.

Treatment of benzene with an alkyl halide and AlCl3


100/114

100

Treatment of benzene with an alkyl halide and AlCl3

places an electron-donor R group on the ring. Since R

groups activate the ring, the alkylated product (C6H5R) is

now more reactive than benzene itself towards furthersubstitution, and it reacts again with RCl to give

products of polyalkylation.

Polysubstitution does not occur with Friedel-Crafts

acylation.

Disubstituted Benzenes


101/114

101

1. When the directing effects of two groups reinforce, the

new substituent is located on the position directed byboth groups.

2 If th di ti ff t f t h


102/114

102

2. If the directing effects of two groups oppose each

other, the more powerful activatorwins out.


103/114

103

3. No substitution occurs between two meta substituents

because of crowding.

Synthesis of Benzene Derivatives


104/114

104

y

In a disubstituted benzene, the directing effects indicate

which substituent must be added to the ring first.

Let us consider the consequences of bromination first

followed by nitration, and nitration first, followed bybromination.

Pathway I, in which bromination precedes nitration, yields the


105/114

105

Pathway I, in which bromination precedes nitration, yields the

desired product. Pathway II yields the undesired meta isomer.

Halogenation of Alkyl Benzenes


106/114

106

Benzylic CH bonds are weaker than most other sp3 hybridized

CH bonds, because homolysis forms a resonance-stabilized

benzylic radical.

As a result, alkyl benzenes undergo selective bromination at the

weak benzylic CH bond under radical conditions to form the

benzylic halide.


107/114

107


108/114

Oxidation and Reduction of Substituted Benzenes


109/114

109

Arenes containing at least one benzylic CH bond are oxidized

with KMnO4 to benzoic acid.

Substrates with more than one alkyl group are oxidized to

dicarboxylic acids. Compounds without a benzylic hydrogen are

inert to oxidation.

Ketones formed as products of Friedel-Crafts acylation can be


110/114

110

reduced to alkyl benzenes by two different methods:

1. The Clemmensen reductionuses zinc and mercury in thepresence of strong acid.

2. The Wolff-Kishner reductionuses hydrazine (NH2NH2) and

strong base (KOH).

We now know two different ways to introduce an alkyl group on a


111/114

111

y y g p

benzene ring:

1. A one-step method using Friedel-Crafts alkylation.2. A two-step method using Friedel-Crafts acylation to form a

ketone, followed by reduction.

Figure 18.8Two methods to prepare an

alkyl benzene

Although the two-step method seems more roundabout, it must be


112/114

112

used to synthesize certain alkyl benzenes that cannot be prepared

by the one-step Friedel-Crafts alkylation because of

rearrangements.

A nitro group (NO2) that has been introduced on a benzene


113/114

113

ring by nitration with strong acid can readily be reduced to

an amino group (NH2) under a variety of conditions.

For next time, 18.21-18.30


114/114

Documents

Electrophillic Aromatci Substitution