Chapter 15

Aromaticity. Reactions of Benzene

Conjugated System vs. Aromatic System

Benzene Structure (C6H6)

H H C C C C H C C H or H H

C-C 0.154 nm C=C 0.134 nm C-C(benzene) 0.139 nm

Br2

Br + Br

Br Br

Br2

no reaction

H /H2O * OH

+ H /H2O

no reaction
Hg(OAc)2

Hg(OAc)2, H2O * OH 1. BH3 2. H2O2, OH-, H2O

no reaction H2O
BH3
* OH

no reaction H2O2, OH-, H2O

3

What is Benzenes Real Structure

P. 641

resonance stabilization energy

P. 642

Aromaticity (15.1 - 15.4)

Criteria for Aromaticity:
Benzene is the typical aromatic compound. It has a VERY high resonance stabilization energy (36 kcal/mol). ALL of the following three criteria MUST be met: (1) The compound must have an uninterrupted cyclic cloud of -electrons above and below the plane of the molecule. In other words, all the atoms in the ring must be usually sp 2 (sometimes sp) hybridized. (2) In order for the sp 2 unhybridized p orbitals to overlap, the molecule must be reasonably planar.

(3) The cloud must have an odd number of pairs of electrons. Benzene has 6 electrons (equaling 3 pairs).

Criteria for Aromaticity (15.1-15.4)

n=0

n=1

n=2

n=3

A compound is antiaromatic if it is a planar, cyclic compound with an uninterrupted ring of cloud, but it contains 4n+2 number of electrons (15.6)

anti-aromatic

aromatic

non-aromatic

p 649
> >
8

PROBLEM: Which of the following are aromatic, antiaromatic or nonaromatic?

14e aromatic

18e aromatic

6e aromatic

10e non-aromatic

4e non-aromatic

4e anti-aromatic

2e non-aromatic

2e aromatic
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4n+2 or 4n # of fully delocalized electrons in in cyclic plane

4e non-aromatic

4e anti-aromatic

6e aromatic

10e aromatic

10e aromatic

14e aromatic

4n+2 or 4n # of fully delocalized electrons in in cyclic plane

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MO Description of Aromaticity and Antiaromaticity (15.7)

antibonding MOs

p orbitals
bonding MOs

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MO Description of Aromaticity and Antiaromaticity (15.7)

Antiaromatic molecules:
antibonding non-bonding bonding

antibonding

bonding bonding

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Aromatic heterocyclic compounds (15.4)

Benzene , pyridine, pyrrole, fur an and thiophene are examples of aromatic molecules .

N benzene pyridine

N H pyrrole

furan

thiophene

N N H indole N quinoline N purine

N N H

Except for benzene, these are heteroaromatic compounds because they have a non-carbon atom in the ring

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P. 646

14

P. 646
They are not as good bases as their saturated counterparts

N H

N H

15

Chemical Consequences of Aromaticity (15.5)

P. 647
H -H+ H H H H resonance hybrid
16

Chemical Consequences of Aromaticity (15.5)

P. 648
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Nomenclature of Monosubstituted Benzenes (15.8)

Many monosubstituted benzenes are named simply by using the name of the substituent, followed by benzene:
Br NO 2 CH2CH3 Cl

bromobenzene

nitrobenzene

ethylbenzene

chlorobenzene

Because of their historical importance, some monosubstituted benzenes have trivial names:
CH3 HO C O CH CH 2 NH2

toluene

benzoic acid

styrene

aniline
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Nomenclature of Monosubstituted Benzenes (15.8)

When a benzene ring is named as a substituent it is called a PHENYL group. Only when it has an extra methyl ene is it called a BENZYL group:
~~~

phenyl group

~ ~ ~

CH2

benzyl group O

O diphenyl ether dibenzyl ether

ARYL is the generic name for a pheny l, or a substituted phenyl gr oup.

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Nomenclature of Monosubstituted Benzenes (15.8)

Alkylbenzenes are named either as alkyl -substituted benzenes OR as phenyl -substituted alkanes:
CH3 H3C C CH3

tert-butylbenzene

3-phenylhexane

C6H5 = phenyl (Ph) group

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How Benzene Reacts (15.9)

H+

E H ADDITION PRODUCT

H E E H

N -H+ E SUBSTITION PRODUCT

E = electrophile N = nucleophile

This is an electrophilic aromatic substitution reaction

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Reaction Coordinate Diagram

p 654
22

General Mechanism - Electrophilic Aromatic Substitution Reactions (15.10)

H E
+

-H+

N H E H SLOW E H E H E FAST E

+ N-H

Very Important to Know What is the Electrophile!

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Common Electrophilic Aromatic Substitution Reactions (15.10)

(1) Halogenation (the H on the benzene ring is replaced by a Br, Cl, or I).
O

Cl

O N

(2) Nitration [the H is replaced with a nitro group (NO 2)]. (3) Sulfonation [the H is replaced with a sulfonic acid group (SO 2OH)]. (4) Friedel-Crafts Acylation [the H is replaced with an acyl group (R-C=O)]. (5) Friedel-Crafts Alkylation (the H is replaced with an alkyl group). The two-step mechanism above applies to all five of these reactions.
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O S

OH O

O R

Halogenation of Benzene (15.11)

This reaction requires a catalyst. It is usually a Lewis acid catalyst.
FeBr3 + Br2 bromobenzene Br + HBr

FeCl3 + Cl2

Cl + chlorobenzene HCl

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Halogenation of Benzene (15.11)

The Electrophile is Halonium

Electrophile (e.g. bromination):

Br Br FeBr3 Br Br FeBr3

Br

FeBr4

The bromoni um ion is the electrophi le (or its adduct with FeBr 4-). In the case of iodination, I2 is usua lly oxidized to I+ using nitr ic acid.

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This reaction requires a catalyst. It is usually a Lewis acid catalyst.

FeBr3 + Br2 bromobenzene Br + HBr

FeCl3 + Cl2

Cl + chlorobenzene HCl

p 656
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Nitration of Benzene (15.12)

The catalyst is sulfuric acid.
H2S O4 + HNO 3 nitrobenzene NO2 + H 2O

nitronium ion H HO NO2 NO2

HO

NO2

OSO3H

+ HSO4

+ H 2O

The nitronium ion is the electrophile.

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The catalyst is sulfuric acid.

H2S O4 + HNO 3 nitrobenzene NO2 + H 2O

nitronium ion H HO NO2 NO2

HO

NO2

OSO3H

+ HSO4

+ H 2O

The nitronium ion is the electrophile.

p 658
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Sulfonation of Benzene (15.13)

+ H2SO4 heat SO3H + H2O

benzenesulfonic acid

HO-SO3H

HO-SO3H

HO-SO3H H

O-SO3H

O H2O + S O OH

Sulfonium ion

The electrophile is SO3H+ (protonate d sulfur trioxide) Sulfonation is reversible if benzenesulfon ic acid is heated in water, de-sulfonation occurs by way of an exact reversal of the sulfona tion mechanis m. This involves the principle of microscopic reversibility (book, page 659).

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H2SO4

heat

SO3H + H2O

benzenesulfonic acid

HO-SO3H

HO-SO3H

HO-SO3H H

O-SO3H

O H2O + S O OH

The electrophile is SO3H+ (protonate d sulfur trioxide)

Sulfonation is reversible if benzenesulfon ic acid is heated in water, de-sulfonation occurs by way of an exact reversal 659 of the sulfona tion mechanis m. This involves the principle of microscopic reversibility (book, page 659).

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32

Friedel-Crafts Acylation of Benzene (15.14)

The reaction uses an acid (acyl) halide or an acid anhydride as the reagent, and the catalyst is a Lewis acid such as AlCl 3.
O + R O C 1. AlCl3 Cl 2. H2O R + HCl

acyl chloride
O + R O C O C 1. AlCl3 R 2. H2O R + O C

OH

acid anhydride

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Friedel-Crafts Acylation of Benzene (15.14)

The Electrophile is the Acylium Ion
O + R O C 1. AlCl3 Cl 2. H2O R + HCl

acyl chloride

O C

+ Cl

AlCl3

R C O

R C O

AlCl4

acylium ion

p 660

34

Friedel-Crafts Acylation of Benzene (15.14)

The Electrophile is the Acylium Ion

The electro phile is an acylium ion, [R-C=O] +.

O C + Cl AlCl3 R C O R C O + AlCl4

acylium ion

The water in the second step is needed to decompose the aluminum salt of the product:
O R AlCl3 O AlCl3 R 3 H2O O R + Al(OH)3 + 3 HCl

35

Friedel-Crafts Alkylation of Benzene (15.15)

R-Cl

AlCl3

R + HCl

The electrophile is a carbocation WATCH out for rearrangements!!!

Cl

+ AlCl3

AlCl4

36

R-Cl

AlCl3

R + HCl

The electrophile is a carbocation WATCH out for rearrangements!!!

Cl

+ AlCl3

AlCl4

p 662

37

Friedel-Crafts Alkylation of Benzene (15.15)

R-Cl

AlCl3

R + HCl

The electrophile is a carbocation WATCH out for rearrangements!!!

Cl

+ AlCl3

AlCl4

38

Friedel-Crafts Alkylation of Benzene (15.15)

All of the previously discussed carbocation rearrangement problems (1,2 alkyl or hydride shifts) apply here.
+ AlCl3 CH3CH2Cl + HCl

CH3CH2CH2CH2Cl

AlCl3 + 35% + HCl 65%

39

Friedel-Crafts Alkylation of Benzene (15.15)

Another example:

p 662

40

Friedel-Crafts Alkylation of Benzene (15.15)

The electro phile can also be generated by protonation of alkenes (usi ng acids with poor nucleophilic counterions):
+ H3C C C CH3 H H
H3C CH CH2 CH3

HF

electrophile

Or alcohols can be protonate d with acid (again, an acid with a poorly nucle ophilic anion) and then deh ydrated:
H2SO4 OH
electrophile
41

OH2

Two Step Alkylation of Benzene: by Acylation and Reduction (15.16)

Because of the p roblemsassociated with carbocation rearrangements and polyalkylation, Friedel-Crafts alkylation of benzene is not very general. However, Friedel-Crafts ACYLATION do es not suffer from rearrangements!
Alkylation:
+ CH3CH2CH2CH2Cl AlCl3 + 35% + HCl 65%

Acylation plus reduction:

O O + Cl 1. AlCl3 2. H2O H2/Pd-C

42

Two Step Alkylation of Benzene by Acylation and Reduction (15.16)

The ke tone carbonyl adjacent to a benzene ring is susceptible to reduction with hydrogen and palladium. There are also two other well-known meth ods for accomplishi ng this reduction: (1) Clemmensen Reductio n [using zinc amalgam, HCl, and heat (note acidic conditions)]. (2) Wolff-Kischner Reduction [using hydrazine, hydroxide, and heat (note basic conditions)].
CLEMMENSEN WOLFF-KISCHNER O

Zn(Hg), HCl heat

H2NNH2, OHheat
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Other Alkylations of Benzene:

by Coupling Reactions (15.17)
Recall these reactions from earlier in the course (organometallic coupling reactions, Section 10.13, pp 469-472). Gilman:
Br + (CH3CH2)2CuLi + CH3CH2Cu + LiBr

Stille:
Br + (CH3CH2CH2) 4Sn Pd(PPh3)4 + (CH3CH2CH2)3SnBr THF

Suzuki:
Cl + B O O Pd(PPh3)4 NaOH O + HO B O

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Problems: What is the major reaction product?

O Cl AlCl3 OO

O CCl

AlCl 3

CH 3 CH 3 CH CH 2CH 2Cl

AlCl 3

HNO 3

H 2SO 4

NO2
45

Problem: Howprepare the following compounds from would you prepare the following How would you
benzene?

molecule from Benzene?

O

AlCl3 O Cl

Zn(Hg),HCl, or H2NNH2,HO-,

AlCl3

Cl

AlCl3 Cl O or anhydride

46

Summary of Electrophilic Substitution Reactions of Benzene

H + E A catalyst E + H A

Br bromination Cl
Br2 FeBr 3

chlorination

Cl 2 FeCl 3
H 2SO 4

RCl AlCl 3

alkylation

SO 3H

HNO

H 2SO 4

O O RCCl CR
AlCl 3

NO 2 sulfonation acylation
47

Thats it!

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