1

Treatment of cyclooctatetrene with potassium gives you a dianion. Classify the starting material and product as aromatic, antiaromatic or nonaromatic?

2 K

2

3

Classify cyclononatetrene and it’s various ions as either aromatic, antiaromatic or nonaromatic.

4

5

Electrophilic Aromatic Substitution

• The characteristic reaction of benzene is electrophilic aromatic substitution—a hydrogen atom is replaced by an electrophile.

Background

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

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 shown below:

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

• The energy changes in electrophilic aromatic substitution are shown below:

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 too violently.

Halogenation

12

• Chlorination proceeds by a similar mechanism.

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

• Generation of the electrophile in nitration requires strong acid.

15

• Generation of the electrophile in sulfonation requires strong acid.

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

• 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

Friedel-Crafts Alkylation and Friedel-Crafts Acylation

19

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

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

[2] Rearrangements can occur.

These results can be explained by carbocation rearrangements.

23

24

Rearrangements can occur even when no free carbocation is formed initially.

25

[3] Other functional groups that form carbocations can also be used as starting materials.

26

Each carbocation can then go on to react with benzene to form a product of electrophilic aromatic substitution. For example:

27

Starting materials that contain both a benzene ring and an electrophile are capable of intramolecular Friedel-Crafts reactions.

28

For Monday, do problems 18.1-18.11.

29

1) Why is benzene less reactive than an alkene?

The pi electrons of benzene are delocalized over 6 atoms, thus making benzene more stable and less available for electron donation.

While an alkene’s electrons are localized between two atoms, thus making it more nucleophillc and more reactive toward electrophiles.

30

2) Show how the other two resonance structures can be deprotonated in step two of electrophillic aromatic substitution.

H

E

BE

H

E

BE

31

H

E

BE

32

3) Draw a detailed mechanism of the chlorination of benzene.

Cl ClFeCl3 Cl Cl FeCl3

Formation of Electrophile

Cl Cl FeCl3

H H

Cl

H

Cl

H

Cl

+ FeCl4

Electrophillic Additon

33

H

Cl FeCl4

Cl

+ HCl + FeCl3

Deprotonation

34

4) Draw stepwise mechanism for the sulfonation of A.

SO3

H2SO4

SO3H

a

b

O

S

O O

H OSO3H SO3H + HSO4

Formation of Electrophile

35

H

SO3H

RR

H

SO3H

R

H

SO3H

R

H

SO3H

Electrophillic Addition

R

H

SO3H

HSO4R

SO3H

+ H2SO4

Deprotonation

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

+AlCl3

H3CH2C

Cl

O

c) O

CH2CH3

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

O

c)

O

Cl

40

7) Draw a stepwise mechanism for the following friedal-Crafts alkylation?

+ CH3CH2Cl

AlCl3

CH2CH3

CH3CH2Cl AlCl3 H3CH2C Cl AlCl3

Formation of Electrophile

41

H3CH2C Cl AlCl3

H

H

CH2CH3

H

CH2CH3

H

CH2CH3

Electrophillic Additoon

H

CH2CH3

AlCl3Cl

CH2CH3

+ HCl + AlCl3

Protonation

42

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

Br

A

Br

B

Br

CBr

D

Br

BBr

D

Look at the carbon to which the halogen is attached and determine its hybridization. If sp2 its unreactive, while sp3 is reactive.

43

9) Draw a stepwise mechanism for the following reaction.

+ (CHe)2CHCH2ClAlCl3

C(CH3)3

+ HCl + AlCl3

H3C

CH3

H

H2C Cl AlCl3 H3C

CH3

H

H2C Cl AlCl3

H3C

CH3

CH3+ AlCl4

Formation of Electrophile

1,2 H shift

44

H3C

CH3

CH3

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

Electrophillic Additon

H C(CH3)3

AlCl4

C(CH3)3

+ AlCl3 + HCl

Deprotonation

45

10) Draw the product of each reaction

+H2SO4

a)

+H2SO4

(H3C)2C CH2

b)

C(CH3)3

46

+H2SO4

OH

c)

+H2SO4

OHd)

47

11) Draw a stepwise mechanism for the intermolecular Friedal-Crafts acylation below

Cl

Cl

OCl

AlCl3

Cl

Cl

O

+ HCl + AlCl3

48

Cl

Cl

OCl

AlCl3

Cl

Cl

OClCl3Al

Cl

Cl

O

Cl

Cl

O+ AlCl4

Formation of Electrophile

49

Cl

Cl

O

Cl

Cl

O

H

Cl

Cl

O

H

Cl

Cl

O

H

Electrophillic addition

50

Cl

Cl

O

HAlCl4

Cl

Cl

O

+ HCl + AlCl3

Deprotonation

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

Considering inductive effects only, the NH2 group withdraws electron density and CH3 donates electron density.

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

• 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 benzene ring by a resonance effect.

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

• The inductive and resonance effects in compounds having the general structure C6H5-Y=Z (with Z more electronegative than Y) are both electron withdrawing.

57

• These compounds represent examples of the general structural features in electron-donating and electron withdrawing substituents.

58

Electrophilic Aromatic Substitution and Substituted Benzenes.

• Electrophilic aromatic substitution is a general reaction of all aromatic compounds, including polycyclic aromatic hydrocarbons, heterocycles, and substituted benzene derivatives.

• A substituent affects two aspects of the electrophilic aromatic substitution reaction:

1. The rate of the reaction—A substituted benzene reacts faster or slower than benzene itself.

2. The orientation—The 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

• Consider toluene—Toluene reacts faster than benzene in all substitution reactions.

• The electron-donating CH3 group activates the benzene ring to electrophilic attack.

• Ortho and para products predominate.

• The CH3 group is called an ortho, para director.

60

• Consider nitrobenzene—It reacts more slowly than benzene in all substitution reactions.

• The electron-withdrawing NO2 group deactivates the benzene ring to electrophilic attack.

• The meta product predominates.

• The NO2 group is called a meta director.

61

All substituents can be divided into three general types:

62

63

• Keep in mind that halogens are in a class by themselves.

• Also note that:

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 a resonance 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

• The principles of inductive effects and resonance effects can now be used to predict carbocation stability.

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

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 charge on the atom bonded to the benzene ring.

69

To evaluate the effects of a given substituent, we can use the following stepwise procedure:

70

• A CH3 group directs electrophilic attack ortho and para to itself because an electron-donating inductive effect stabilizes the carbocation intermediate.

71

• An NH2 group directs electrophilic attack ortho and para to itself because the carbocation intermediate has additional resonance stabilization.

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

Figure 18.7 The reactivity and directing

effects of common substitutedbenezenes

74

For Wednesday:

Draw out stepwise mechanisms for 10b and c.

18.12-18.20 as well.

10b)

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

+H2SO4

(H3C)2C CH2

C(CH3)3

Formation of Electrophile

Electrophillic Addition

C(CH3)3

C(CH3)3 C(CH3)3

C(CH3)3

HH H

H

C(CH3)3

HHSO4

C(CH3)3

+ H2S04

Deprotonation

10c)

+H2SO4

OH

OH H O SO3H OH2

+ HSO4

+ H2O + HSO4

Formation of Electrophile

HH H

H

Electrophillic Addition

H

HSO4

Deprotonation

12)Identify each group as having an electron 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 determine whether there is an electron donating or withdrawing resonance effect.

OCH3 OCH3 OCH3OCH3

OCH3

OCH3a)

Negative charge on ring, electron donating effect

b)O

O OO

O

OO

O

Positive charge, electron withdrawing

14)Identify as electron donating or electron withdrawing.

a)OCH3

Lone pair on oxygen, electron donating

b) I Halogen, electron withdrawing

c) C(CH3)3 Alkyl group, electron donating

OCH3

CH3CH2Cl

AlCl3

15)Predict the products.

a)OCH3

CH2CH3

+

OCH3

H3CH2C

b)Br

HNO3

H2SO4

Br

NO2

+

Br

O2N

c)NO2

Cl2

FeCl3

NO2

Cl

16)Predict the products when reacted with HNO3 and H2SO4. Also state whether the reactant is more or less reactive than benzene.

a) OO

NO2

N

b)N

O2N

Less

Less

Cl

c)

Cl

NO2

+

Cl

O2N

Less

d)

OHOH

NO2

+

OH

O2N

More

CH2CH3CH2CH3

NO2

+

CH2CH3

O2N

More

d)

17)Label each compound as less or more reactive than benzene.

a)C(CH3)3

more

OH

OH

b)

more

c)O

OCH2CH3 less

N(CH3)3

d)

less

18) Rank each group in order of increasing reactivity.

Cl OCH3

a)

2 3 1

NO2 CH3

b)

2 3 1

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

b)OH

OH

NO2

OH

NO2

OH

NO2

OH

NO2

OH

NO2

Most stable

c) O

O

NO2

O

NO2

O

NO2

O

NO2

O

NO2

Vey unstable

20) Show why chlorine is an ortho para director. Cl

E

Cl

E

Cl

E

Cl

E

Cl

E

Especially stable, every atom has an octet

Cl

E

Cl

E

Cl

E

Cl

E

Cl

E

Cl

E

Cl

E

Cl

E

Especially stable, every atom has an octet

98

Limitations in Electrophilic Aromatic Substitutions

• Benzene rings activated by strong electron-donating groups—OH, NH2, and their derivatives (OR, NHR, and NR2)—undergo polyhalogenation when treated with X2 and FeX3.

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.

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 further substitution, and it reacts again with RCl to give products of polyalkylation.

• Polysubstitution does not occur with Friedel-Crafts acylation.

101

Disubstituted Benzenes

1. When the directing effects of two groups reinforce, the new substituent is located on the position directed by both groups.

102

2. If the directing effects of two groups oppose each other, the more powerful activator “wins out.”

103

3. No substitution occurs between two meta substituents because of crowding.

104

Synthesis of Benzene Derivatives

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 by bromination.

105

Pathway I, in which bromination precedes nitration, yields the desired product. Pathway II yields the undesired meta isomer.

106

Halogenation of Alkyl Benzenes

Benzylic C—H bonds are weaker than most other sp3 hybridized C—H bonds, because homolysis forms a resonance-stabilized benzylic radical.

As a result, alkyl benzenes undergo selective bromination at the weak benzylic C—H bond under radical conditions to form the benzylic halide.

107

108

Note that alkyl benzenes undergo two different reactions depending on the reaction conditions:

• With Br2 and FeBr3 (ionic conditions), electrophilic aromatic substitution occurs, resulting in replacement of H by Br on the aromatic ring to form ortho and para isomers.

• With Br2 and light or heat (radical conditions), substitution of H by Br occurs at the benzylic carbon of the alkyl group.

109

Oxidation and Reduction of Substituted Benzenes

Arenes containing at least one benzylic C—H 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.

110

Ketones formed as products of Friedel-Crafts acylation can be reduced to alkyl benzenes by two different methods:

1. The Clemmensen reduction—uses zinc and mercury in the presence of strong acid.

2. The Wolff-Kishner reduction—uses hydrazine (NH2NH2) and strong base (KOH).

111

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

112

Although the two-step method seems more roundabout, it must be used to synthesize certain alkyl benzenes that cannot be prepared by the one-step Friedel-Crafts alkylation because of rearrangements.

113

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