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Chapter 15

Aromaticity.

Reactions of Benzene

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Conjugated System vs. Aromatic System

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Benzene Structure (C6H6)

Br2

Br

Br

Br

Br+

H+/H2O

OH*

Hg(OAc)2, H2O

OH*

1. BH3

OH*2. H2O2, OH-, H2O

CC

CC

C

C

H

H

H

H

H

H

or

Br2

H /H2O+

Hg(OAc)2

BH3

H2O

H2O2, OH-, H2O

no reaction

no reaction

no reaction

no reaction

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

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What is Benzene’s Real Structure

P. 641

5

P. 642

resonance stabilization energy

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Criteria for Aromaticity:Benzene is the typical aromatic compound. It has a VERYhigh resonance stabilization energy (36 kcal/mol). ALL ofthe following three criteria MUST be met:

(1) The compound must have an uninterrupted cycliccloud of -electrons above and below the plane of themolecule. In other words, all the atoms in the ring must beusually sp2 (sometimes sp) hybridized.

(2) In order for the sp2 unhybridized “p” orbitals tooverlap, 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).

Aromaticity (15.1 - 15.4)

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Criteria for Aromaticity (15.1-15.4)

Hückel’s rule says an aromatic molecule must have (4n+2) -electrons – this statement is exactly the same as saying an odd number of pairs of -electrons. So aromatic molecules can have a total of 2 or 6 or 10 or 14 etc., -electrons, thus fulfilling Hückel’s rule for “n” = 0, 1, 2, 3, etc. Examples:

n = 0 n = 1 n = 2 n = 3

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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)

p 649

> >

anti-aromatic aromatic non-aromatic

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

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

14earomatic

18earomatic

6earomatic

10enon-aromatic

4enon-aromatic

2e

aromatic

4e

anti-aromatic

2e

non-aromatic

10

+ : -

4enon-aromatic

4eanti-aromatic

6earomatic

14earomatic

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

10earomatic10e

aromatic

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MO Description of Aromaticity and Antiaromaticity (15.7)

Benzene, an aromatic molecule, has six p atomic orbitals which combine to produce 6 MOs: three bonding MOs and three antibonding MOs. Two of the bonding MOs are degenerate (i.e. of the same energy).

antibonding MOs

bonding MOs

p orbitals

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MO Description of Aromaticity and Antiaromaticity (15.7)

Antiaromatic molecules:

H

bonding

non-bonding

antibonding

antibonding

bonding

bonding

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Aromatic heterocyclic compounds (15.4) Benzene, pyridine, pyrrole, furan and thiophene are examples of aromatic molecules.

NNH

benzene pyrrolepyridine

O

furan

S

thiophene

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

N NH

N

N N

N

H

indole quinoline purine

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P. 646

15NH

NH O S

They are not as good bases as their saturated counterparts

P. 646

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Chemical Consequences of Aromaticity (15.5)

H H H

H

H

resonancehybrid

-H+

P. 647

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Chemical Consequences of Aromaticity (15.5)

P. 648

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Nomenclature of Monosubstituted Benzenes (15.8)

Many monosubstituted benzenes are named simply byusing the name of the substituent, followed by “benzene”:

Br NO2 CH2CH3 Cl

bromobenzene nitrobenzene ethylbenzene chlorobenzene

Because of their historical importance, somemonosubstituted benzenes have trivial names:

CH3 C CH NH2

toluene benzoic acid styrene aniline

OHO CH2

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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 methylene is it called a BENZYL group:

CH2

~~~~ ~ ~

phenyl group benzyl group

OO

diphenyl ether dibenzyl ether ARYL is the generic name for a phenyl, or a substituted phenyl group.

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Nomenclature of Monosubstituted Benzenes (15.8)

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

C

tert-butylbenzene 3-phenylhexane

CH3

CH3

H3C

C6H5 = phenyl (Ph) group

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How Benzene Reacts (15.9)Benzene is electron-rich because of its -electrons: it is nucleophilic so it attacks electrophiles to give initially a carbocation intermediate (“benzenonium ion”) which loses a proton thus regaining its aromatic stability.

EH

EH N

H

EN H

-H+

E

E = electrophile

N = nucleophile

ADDITION PRODUCT

SUBSTITION PRODUCT

This is an electrophilic aromatic substitution reaction

H+

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Reaction Coordinate Diagram

p 654

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General Mechanism - Electrophilic Aromatic Substitution Reactions (15.10)

EE

HH

EE

H

E

H

N

+ N-H

SLOW FAST

Very Important to Know What is the Electrophile!

HE+

E

-H+

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Common Electrophilic Aromatic Substitution Reactions (15.10)

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

(2) Nitration [the H is replaced with a nitro group (NO2)].

(3) Sulfonation [the H is replaced with a sulfonic acidgroup (SO2OH)].

(4) Friedel-Crafts Acylation [the H is replaced with anacyl group (R-C=O)].

(5) Friedel-Crafts Alkylation (the H is replaced with analkyl group).

The two-step mechanism above applies to all five of thesereactions.

Cl

NO

O

SO

OHO

R

O

R

H

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Halogenation of Benzene (15.11)

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

Br+ Br2

FeBr3

bromobenzene

Cl+ Cl2

FeCl3

chlorobenzene

+ HBr

+ 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 “bromonium ion” is the electrophile (or its adduct with FeBr4

-). In the case of iodination, I2 is usually oxidized to I+ using nitric acid.

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p 656

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Nitration of Benzene (15.12)

The catalyst is sulfuric acid.

NO2+ HNO3

H2SO4

nitrobenzene

+ H2O

HO NO2 H OSO3H+ HOH

NO2

+ HSO4

NO2

+ H2O

nitroniumion

The “ nitronium ion” is the electrophile.

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p 658

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Sulfonation of Benzene (15.13)SO3H

+ H2SO4

benzenesulfonic acid

+ H2Oheat

HO-SO3H HO-SO3H HO-SO3HH

O-SO3H+ +

H2O + S OH

O

O The electrophile is SO3H

+ (protonated sulfur trioxide) Sulfonation is reversible – if benzenesulfonic acid is heated in water, de-sulfonation occurs by way of an exact reversal of the sulfonation mechanism. This involves the principle of microscopic reversibility (book, page 659).

Sulfonium ion

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p 659

32

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Friedel-Crafts Acylation of Benzene (15.14)

+ + HClO

CClR

1. AlCl3

2. H2O

acyl chloride

R

O

+O

COR

1. AlCl3

2. H2O

acid anhydride

R

O

C

O

R

O

COHR

+

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O

CClR

AlCl3+ C OR C OR + AlCl4

acylium ion

+ + HClO

CClR

1. AlCl3

2. H2O

acyl chloride

R

O

p 660

Friedel-Crafts Acylation of Benzene (15.14)The Electrophile is the “Acylium Ion”

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Friedel-Crafts Acylation of Benzene (15.14)The Electrophile is the “Acylium Ion”

The electrophile is an “acylium ion”, [R-C=O]+. The water in the second step is needed to decompose the aluminum salt of the product:

R

O

AlCl3R

OAlCl3

R

O

+ Al(OH)3 + 3 HCl3 H2O

O

CClR

AlCl3+ C OR C OR + AlCl4

acylium ion

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Friedel-Crafts Alkylation of Benzene (15.15)

R+ + HCl

AlCl3R-Cl

The electrophile is a carbocation – WATCH out forrearrangements!!!

R Cl AlCl3+ R + AlCl4

37p 662

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Friedel-Crafts Alkylation of Benzene (15.15)

R+ + HCl

AlCl3R-Cl

The electrophile is a carbocation – WATCH out forrearrangements!!!

R Cl AlCl3+ R + AlCl4

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Friedel-Crafts Alkylation of Benzene (15.15)

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

AlCl3CH3CH2Cl

+

+ HCl

AlCl3CH3CH2CH2CH2Cl

+

35% 65%

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Friedel-Crafts Alkylation of Benzene (15.15)

Another example:

p 662

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The electrophile can also be generated by protonation of alkenes (using acids with poor nucleophilic counterions): Or alcohols can be protonated with acid (again, an acid with a poorly nucleophilic anion) and then dehydrated:

Friedel-Crafts Alkylation of Benzene (15.15)

CHH3C CH2 CH3

+HF

CH

CH

CH3H3C

+

OH

H2SO4

OH2+

electrophile

electrophile

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

+

+ HCl

AlCl3CH3CH2CH2CH2Cl

+

35% 65%

+2. H2OCl

OO

H2/Pd-C

1. AlCl3

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

O

Zn(Hg), HClheat

H2NNH2, OH-

heat

CLEMMENSEN WOLFF-KISCHNER

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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

+ CH3CH2Cu + LiBr(CH3CH2)2CuLi

Stille:

+Br

(CH3CH2CH2)4SnPd(PPh3)4

THF(CH3CH2CH2)3SnBr+

Suzuki:

Cl Pd(PPh3)4

NaOH

OB

O

+ +O

BO

HO

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Cl

O

OAlCl3

Problems: What is the major reaction product?

+OCCl

AlCl3

+ HNO3H2SO4

+CH3

CHCH3

CH2CH2ClAlCl3

O

O

NO2

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Problem: How would you prepare the following molecule from Benzene?

Cl

O

AlCl3

O

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

AlCl3

Cl

Cl

AlCl3

Oor anhydride

O

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H E

+ E A catalyst + H A

Br

NO2

R

CR

Cl

SO3HOH2SO4 O

RCCl

AlCl3

AlCl3

RClFeCl3

Cl2Br2 FeBr3

HNO3 H2SO4

chlorination alkylation

sulfonation acylation

bromination

Summary of Electrophilic Substitution Reactions of Benzene

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That’s it!