9 9-1 copyright © 2000 by john wiley & sons, inc. all rights reserved. introduction to organic...

99

9-9-11Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.

Introduction to Introduction to Organic Organic

ChemistryChemistry2 ed2 ed

William H. BrownWilliam H. Brown

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AromaticAromatic

CompoundsCompoundsChapter 9Chapter 9

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Benzene - Kekulé Benzene - Kekulé • The first structure for benzene was proposed by

August Kekulé in 1872

• this structure, however, did not account for the unusual chemical reactivity of benzene

C

H

C

H

C

H

C

HC

H

C

H

C

C

C

C

C

C

H

H

HH

HH

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Benzene - VB ModelBenzene - VB Model• The concepts of hybridization of atomic orbitals

and the theory of resonance, developed in the 1930s, provided the first adequate description of benzene’s structure• the carbon skeleton is a regular hexagon, with all C-

C-C and H-C-C bond angles 120°

sp2

-sp2

σ σ

sp2

-1s1.09 Å

120°

120°

120°

1.39 Å

C

C

C

C

C C

H

H H

H

H H

99


Benzene - VB ModelBenzene - VB Model• each carbon has one unhybridized 2p orbital containing

one electron• overlap of the six parallel 2p orbitals forms a

continuous pi cloud • the electron density of benzene lies in one torus above

the plane of the ring and a second below it

C

C

C

C

C C

H

H H

H

H H

99


Benzene - Resonance Benzene - Resonance • We often represent benzene as a hybrid of two

equivalent Kekulé structures• each makes an equal contribution to the hybrid, and

thus the C-C bonds are neither double nor single, but something in between

99


Benzene - ResonanceBenzene - Resonance• Resonance energyResonance energy: the difference in energy

between a resonance hybrid and the most stable of its hypothetical contributing structures in which electrons are localized on particular atoms and in particular bonds

• One way to estimate the resonance energy of benzene is to compare the heats of hydrogenation of benzene and cyclohexene

99


Benzene - ResonanceBenzene - Resonance

• comparing 3 x H° for cyclohexene with H° for benzene, it is estimated that the resonance energy of benzene is approximately 36 kcal/mol

Cyclohexene C yclohexane

Ni

1-2 atm.

° = -28.6 /H kcal mol

(-120 / )kJ mol

+ H2

C yclohexaneBenzene

200-300 atm

Ni

° = -49.8 /H kcal mol

(-208 / )kJ mol

+ 3 H 2

99


Heterocyclic AromaticsHeterocyclic Aromatics• Heterocyclic compoundHeterocyclic compound: contains one or more

atoms other than carbon in a ring• Pyridine and pyrimidine are heterocyclic analogs

of benzene. Each is aromatic.

••••

P yridine Pyrimidine

1

2

3

4

5

6

5

1

2

3

4

6

N

N

N

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PyridinePyridine• Pyridine has a resonance energy of 32 kcal/mol,

slightly less than that of benzene

N

•

•

•

•

•

•

this sp2

hybrid orbital is

perpendicular to the six

2p orbitals of the pi system

this pair of electrons

is not a part of the

aromatic sextet

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FuranFuran• Of the two unshared pairs of electrons on the

oxygen atom of furan, one is and one is not a part of the aromatic sextet• the resonance energy of furan is 16 kcal/mol

•

this pair of

electrons

is not

•

• • O

this pair of electrons

is a part of the

aromatic sextet

99


Other HeterocyclicsOther Heterocyclics

Purine

Indole

N

N

NN

N

H

H

N

H

C H2

C H2

N H2

Serotonin

(a neurotransmitter)

H O

Adenine

N

NN

N

N H2

H

99


NomenclatureNomenclature• Monosubstituted alkylbenzenes are named as

derivatives of benzene• many common names are retained

B enzene

T oluene C umene

E thylbenzene

S tyrene

CH2

CH3

CH3

CH(CH3

)2

CH=CH2

99


NomenclatureNomenclature• these common names are also retained

Phenol A niline

B enzoic acid A nisole

CO2

H

NH2

OCH3

OH

B enzaldehyde

CHO

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NomenclatureNomenclature• benzyl and phenyl groups

Benzene P henyl

group

Toluene B enzyl group

CH3

CH2

-

(Z)-2-Phenyl-2-butene

C6

H5

C C

CH 3

H3

C H

C 6 H 5 CH 2 Cl

Benzyl chloride

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Disubstituted BenzenesDisubstituted Benzenes• Locate the two groups by numbers or by the

locators orthoortho (1,2-), metameta (1,3-), and parapara (1,4-)• where one group imparts a special name, name the

compound as a derivative of that molecule

2-Nitrobenzoic acid

(o-Nitrobenzoic acid )

3-Chloroaniline

(m-Chloroaniline)

4-Bromotoluene

(p-Bromotoluene)

CH3 CO

2H

Br

NO2

Cl

NH2

99


Disubstituted BenzenesDisubstituted Benzenes• where neither group imparts a special name, locate the

groups and list them in alphabetical order

1-Bromo-2-nitrobenzene

(o-Bromonitrobenzene)

1-Chloro-4-ethylbenzene

(p-Chloroethylbenzene)

CH2

CH3

Cl

Br

NO2

1

2

3

4 2

1

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Polysubstituted DerivsPolysubstituted Derivs• if one group imparts a special name, name the molecule

as a derivative of that compound• if no group imparts a special name, list them in

alphabetical order, giving them the lowest set of numbers

6

54

3

2

1

5

6

4

3

21

2,4,6-Tribromophenol 2-Bromo-1-ethyl-4-nitrobenzene

OH

Br

Br

Br

NO 2

CH2

CH3

Br

99


PAHsPAHs• Polynuclear aromatic hydrocarbons (PAHs)

contain two or more aromatic rings, each pair of which shares two ring carbons

PhenanthreneAnthraceneNaphthalene

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PAHsPAHs

CoroneneBenzo[a]pyrene

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PhenolsPhenols• The functional group of a phenol is an -OH group

bonded to a benzene ring

1,2-Benzenediol

(Catechol)

1,4-Benzenediol

(Hydroquinone)

3-Methylphenol

(m-Cresol)

Phenol

OH OH

OH OH

OHCH3

OH

99


Acidity of PhenolsAcidity of Phenols• Phenols are significantly more acidic than

alcohols, compounds that also contain the -OH group

Phenol: pKa

= 9.95

Ethanol: pKa

= 15.9

OH O-

CH3

CH2

O -

CH3

CH2

OH

H2

O+

H2

O+

H3

O+

+

H3

O+

+

99


Acidity of PhenolsAcidity of Phenols• We account for the increased acidity of phenols

relative to alcohols in the following way• delocalization of the negative charge on a phenoxide

ion stabilizes it relative to an alkoxide ion• because a phenoxide ion are more stable than an

alkoxide ion, phenols are stronger acids than alcohols

• Note that while this reasoning helps us to understand why phenols are more acidic than alcohols, it does not give us any way to predict how much stronger they are

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Acidity of PhenolsAcidity of Phenols•• ••

•• •• ••

••••

••

These 2 Kekulé structures

are equivalent

These three contributing structures

delocalize the negative charge onto

carbon atoms of the ring

H

O

H

H

OO

OO

99


Acidity of PhenolsAcidity of Phenols• Ring substituents, particularly halogen and nitro

groups, have marked effects on the acidity of phenols

pKa

9.18

P henol

pKa

9.95

O H O H

C l

p-Chloro-

phenol

pKa

7.15

O H

N O 2

p-Nitro-

phenol

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Acidity of PhenolsAcidity of Phenols• Phenols are weak acids and react with strong

bases to form water-soluble salts• water-insoluble phenols dissolve in NaOH(aq)

Phenol

S odium

hydroxide

S odium phenoxide

W ater

pKa

= 9.95

pKa

= 15.7

(stronger acid)

(weaker acid)

(stronger base)

(weaker base)

OH

O-

Na+

+ NaOH

+ H2

O

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Acidity of PhenolsAcidity of Phenols• most phenols do not react with weak bases such as

NaHCO3; they do not dissolve in aqueous NaHCO3

(Weaker base)

(Weaker acid)

pKa

= 6.36

C arbonic acidS odium phenoxide

(Stronger base)

(Stronger acid)

pKa

= 9.95

Sodium

bicarbonatePhenol

OH

O-

Na+

+ NaHCO3

+ H2

CO3

99


Benzylic OxidationBenzylic Oxidation• Benzene is unaffected by strong oxidizing agents

such as H2CrO4 and KMnO4

• halogen and nitro substituents are unaffected by these reagents

• an alkyl group with at least one hydrogen on the benzylic carbon are oxidized to a carboxyl group

2-Chloro-4-nitro-

toluene

2-Chloro-4-nitro-

benzoic acid

C l

C O2

HC H3

C l

H2

S O4

K2

C r2

O7

O2

N O2

N

99


Benzylic OxidationBenzylic Oxidation• if there is more than one alkyl group, each is oxidized to

a -CO2H group

1,4-Dimethylbenzene

(p-xylene)

1,4-Benzenedicarboxylic acid

(terephthalic acid)

C H3

H2

S O4

K2

C r2

O7

H3

C C O HH O C

O O

99


Rexns of BenzeneRexns of Benzene• The most characteristic reaction of aromatic

compounds is substitution at a ring carbon

+ +

Chlorobenzene

Halogenation:

H ClCl2

FeCl 3HCl

++

Nitrobenzene

Nitration:

H NO2

HNO3

H2

SO4

H2

O

99


Rexns of BenzeneRexns of Benzene

+

Benzenesulfonic acid

Sulfonation:

H SO3

HSO3

H2

SO4

++

An alkylbenzene

Alkylation:

H RRXAlX

3HX

++

Acylation:

An acylbenzene

O

C RH

O

R C XA l X

3H X

99


Rexns of Benzene - EASRexns of Benzene - EAS• Electrophilic aromatic substitutionElectrophilic aromatic substitution: a reaction in

which a hydrogen atom of an aromatic ring is replaced by an electrophile

• We study• several common types of electrophiles, • how each is generated, and • the mechanism by which it replaces hydrogen

++

H E

E+

H+

99


ChlorinationChlorination• Halogenation requires a Lewis acid catalyst, such

as AlCl3 or FeCl3

• Step 1: formation of a chloronium ion

+-

+••

••

••

••

••

••

+••

••

••

••

C l

C l

C l

C l

C l

C l

C lF eC l

C l F e

C l C l F e C l4

-

chloronium

ion

99


ChlorinationChlorination• Step 2: attack of the chloronium ion on the ring to give

a resonance-stabilized cation intermediate

+

+

+

Resonance-stabilized cation intermediate

+

rate-limiting

step

C l

HH

C l

H

C l

C l +

99


ChlorinationChlorination• Step 3: proton transfer to regenerate the aromatic

character of the ring

• The mechanism for bromination is the same as that for chlorination

Chlorobenzene

fast

Cation

intermediate

++

-

+

C l

C l

H

H C l F e C l 3

C l F e C l3

99


EAS: General MechanismEAS: General Mechanism• A general mechanism

• General question: what is the electrophile in an EAS and how is it generated?

+ E+

HE

H

+ rate-

limiting stepStep 1:

Step 2:

E

H

+

fast+ H

+E

Electro-

phileResonance-stabilized

cation intermediate

99


NitrationNitration• The electrophile is NO2

+, generated as follows

+••

•• ••

++

Nitric acid

H O NO2

O SO3

HH O NO2

H

H

HSO4

+•• ••+

•• ••

+

Nitronium ion

O

H

H NO2

H O

H

O=N=O

99


NitrationNitration• The particular value of nitration is that the nitro

group can be reduced to a 1° amino group

4-Aminobenzoic acid

4-Nitrobenzoic acid

+

+

(3 atm)

O2

N CO2

H

CO2

HH2

N 2 H2

O

3 H2

Ni

99


Friedel-Crafts AlkylationFriedel-Crafts Alkylation• Friedel-Crafts alkylation forms a new C-C bond

between a benzene ring and an alkyl group

+

Benzene 2-Chloropropane

(Isopropyl chloride)

Cumene

(Isopropylbenzene)

C H3

A l C l3

C H3

C H C l

C H ( C H 3 ) 2+ H C l

99


Friedel-Crafts AlkylationFriedel-Crafts Alkylation• Step 1: formation of an alkyl cation as an ion pair

An ion pair

containing

a carbocation

+

••

••

••

•• -+

C l C lA l

C l

C l

C l

C l

A l C lC l

R

R R+

A l C l4

-

99


Friedel-Crafts AlkylationFriedel-Crafts Alkylation• Step 2: attack of the alkyl cation on the aromatic ring

+ R+

R

H

R

H

R

H

The positive charge is delocalized onto

three atoms of the ring

+

+

+

99


Friedel-Crafts AlkylationFriedel-Crafts Alkylation• Step 3: proton transfer to regenerate the aromatic

character of the ring

R

H

C l A l C l3

R + + H C lA l C l3

+

99


Friedel-Crafts AcylationFriedel-Crafts Acylation• Friedel-Crafts acylation forms a new C-C bond

between a benzene ring and an acyl group

+

Benzene A cetophenoneAcetyl

chloride

C C H 3O

O

A l C l3

C H3

C C l + H C l

99


Friedel-Crafts AcylationFriedel-Crafts Acylation• the electrophile is an acylium cation

An ion pair

containing

an acylium ion

+-••

••

••

••

+

C l

C l

R - C C l

O

C l A l C l

C l

C l

O

R - C

A l - C l

R - C+

A l C l4

-

O

99


Other AlkylationsOther Alkylations• Carbocations are generated by

• treatment of an alkene with a protic acid, most commonly H2SO4, H3PO4, or HF/BF3

B enzene Propene

(Propylene)

Isopropylbenzene

(Cumene)

C H ( C H3

)2

H3

P O4

+ C H3

C H = C H2

99


Other AlkylationsOther Alkylations• by treating an alkene with a Lewis acid

• and by treating an alcohol with H2SO4 or H3PO4

+

Benzene Cyclohexene Phenylcyclohexane

A l C l3

+

Benzene

( C H 3 ) 3 C O H

H3

P O4

C ( C H 3 ) 3 + H 2 O

tert- Butyl

alcohol

tert -Butylbenzene

99


DisubstitutionDisubstitution• Existing groups on benzene ring influence further

substitution in both orientationorientation and raterate• Orientation:

• certain substituents direct preferentially to ortho & para positions; others direct preferentially to meta positions

• substituents are classified as either

ortho-para directing ortho-para directing or meta directingmeta directing

99


DisubstitutionDisubstitution• Rate:

• certain substituents cause the rate of a second substitution to be greater than that for benzene itself; others cause the rate to be lower

• substituents are classified as • activatingactivating toward further substitution, or • deactivatingdeactivating

99


DisubstitutionDisubstitution• -OCH3 is ortho-para directing

p-Bromo-

anisole

(96%)

o-Bromo-

anisole

(4%)

Anisole

++

OCH3

OCH3

OCH3

Br

Br

Br2

CH3

CO2

H

HBr

99


DisubstitutionDisubstitution• -NO2 is meta directing

m-Dinitro-

benzene

(93%)

Nitro-

benzene

+

++

o-Dinitro-

benzene

p-Dinitro-

benzene

Less than 7% combined

NO2

NO 2

NO2

NO 2

NO2

NO2

NO2

HNO3

H2

SO4

99


DisubstitutionDisubstitution

Weakly

activating

Weakly

deactivating••

••

••

••

••

••

••

••

••

••

••

••

••

••••

••

••••••••

Moderately

activating

Strongly

activatingN H

2N H R N R

2O H

N H C R

O R

O C A rO C R

R

F C l B r I

O O O

99



Strongly

deactivating

Moderately

deactivating

C H

O OO

C R C O H

S O H

C O R

O

O

C N H2

O

O

N O2 N H

3

+C F

3C C l

3

C N

99


DisubstitutionDisubstitution• From the information in Table 9.2, we can make

these generalizations• alkyl groups, phenyl groups, and all groups in which

the atom bonded to the ring has an unshared pair of electrons are ortho-para directing. All other groups are meta directing

• all ortho-para directing groups except the halogens are activating toward further substitution. The halogens are weakly deactivating

99



m-Nitrobenzoic

acid

p-Nitrobenzoic

acid

CH3

CH3

NO2

CO2

H

NO2

CO2

H

NO2

CO2

H

HNO3

H2

SO4

K2

Cr2

O7

H2

SO4

HNO3

H2

SO4

K 2 Cr 2 O 7

H2

SO4

99


Theory of Directing EffectsTheory of Directing Effects• The rate of EAS is limited by the slowest step in

the mechanism• for almost every EAS, the rate-limiting step is attack of

E+ on the aromatic ring to form a resonance-stabilized cation intermediate

• the more stable this cation intermediate, the faster the rate-limiting step and the faster the overall reaction

99


Theory of Directing EffectsTheory of Directing Effects• For ortho-para directors, ortho-para attack forms

a more stable cation than meta attack• ortho-para products are formed faster than meta

products

• For meta directors, meta attack forms a more stable cation than ortho-para attack• meta products are formed faster than ortho-para

products

99


Theory of Directing EffectsTheory of Directing Effects• -OCH3; assume meta attack

OCH3

NO2

+

OCH3

NO2

H

OCH3

NO2

H

OCH3

NO2

H

slow

fast

-H+

+

OCH3

NO2+

++

(a) (b) (c)

99


Theory of Directing EffectsTheory of Directing Effects• -OCH3: assume ortho-para attack

OCH3

NO2

+

fast

+

(d) (e) (f)

OCH3

H NO2

OCH3

H NO2

OCH3

H NO2

OCH3

H NO2

OCH3

NO2

-H+

+

slow

+

+

+

(g)

99


Theory of Directing EffectsTheory of Directing Effects• -NO2; assume meta attack

NO2

NO2

+

NO2

NO 2

H

NO2

NO 2

H

NO2

NO 2

H

slow

fast

-H+

+

NO2

NO 2+

++

(a) (b) (c)

99


Theory of Directing EffectsTheory of Directing Effects• -NO2: assume ortho-para attack

NO2

NO 2

+

fast

+

(d) (e)

NO2

H NO2

NO2

H NO2

NO2

H NO2

NO2

NO2

-H++

slow

+

+

(f)

99


AromaticAromatic

CompoundsCompoundsEnd Chapter 9End Chapter 9

9 9-1 copyright © 2000 by john wiley & sons, inc. all rights reserved. introduction to organic...

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