21-21-11

Chapter 21, BenzeneChapter 21, Benzene and and the Concept ofand and the Concept ofAromaticityAromaticity

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Benzene - Kekulé Benzene - Kekulé

In 1872, August Kekulé proposed the following structure for benzene.

This structure, however, did not account for the unusual chemical reactivity of benzene.

CH

CH

CH

CHC

H

CH

CCC

CCC

H

HHH

HH

21-21-33

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.

Benzene as a hybrid of two equivalentcontributing structures

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Benzene - Resonance ModelBenzene - Resonance 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 planar regular hexagon.• All C-C-C and H-C-C bond angles 120°.

sp2-sp2

sp2-1s109 pm

120°

120°120°

139 pm

C

C

C

C

C CH

H H

H

H H

21-21-55

The Pi System of BenzeneThe Pi System of Benzene

• (a) The carbon framework with the six 2p orbitals.• (b) Overlap of the parallel 2p orbitals forms one torus

above the plane of the ring and another below it• this orbital represents the lowest-lying pi-bonding

molecular orbital.

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Benzene-Molecular Orbital ModelBenzene-Molecular Orbital Model

The molecular orbital representation of the pi bonding in benzene.

21-21-77

Orbitals of the pi System of BenzeneOrbitals of the pi System of BenzeneNumber of nodal surfaces

0

1

2

3

21-21-88

Benzene - ResonanceBenzene - Resonance

Resonance energy:Resonance energy: The difference in energy between a resonance hybrid in which the electrons are delocalized

and the most stable one 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.

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Benzene- Resonance EnergyBenzene- Resonance Energy

Experimental data

Model

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Concept of AromaticityConcept of Aromaticity

The underlying criteria for aromaticity were recognized in the early 1930s by Erich Hückel, based on molecular orbital (MO) calculations.

To be aromatic, a compound must• Be cyclic.• Have one p orbital on each atom of the ring.• Be planar or nearly planar so that there is continuous

or nearly continuous overlap of all p orbitals of the ring.

• Have a closed loop of (4n + 2) pi electrons in the cyclic arrangement of p orbitals.

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Frost CirclesFrost Circles

Frost circle:Frost circle: A graphic method for determining the relative order of pi MOs in planar, fully conjugated monocyclic compounds.• Inscribe in a circle a polygon of the same number of

sides as the ring to be examined such that one of the vertices of the polygon is at the bottom of the circle.

• The relative energies of the MOs in the ring are given by where the vertices of the polygon touch the circle.

Those MOs• Below the horizontal line through the center of the ring

are bonding MOs.• on the horizontal line are nonbonding MOs.• above the horizontal line are antibonding MOs.

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Frost CirclesFrost Circles

• Frost circles describing the MOs for monocyclic, planar, fully conjugated four-, five-, and six-membered rings.

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Relationship of hexa-1,3,5-triene to benzene

How does the linear triene relate to benzene?

?

Relationship of hexa-1,3,5-triene to benzene

?

Relationship of hexa-1,3,5-triene to benzene

?

Look at orbitals 2 and 3.

2

3

Curve around

Antibonding, destabilizing

Bonding, stabilizing

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Aromatic HydrocarbonsAromatic Hydrocarbons

Annulene:Annulene: A cyclic hydrocarbon with a continuous alternation of single and double bonds.• [14]Annulene is aromatic according to Hückel’s

criteria.

[14]Annulene (aromatic)

HH

HH

H

H

H

H

HH

H

H

H H

n = 3

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Aromatic HydrocarbonsAromatic Hydrocarbons

• [18]Annulene is also aromatic.

[18]Annulene (aromatic)

H

H

HH

HH

H

H

HH

H

HH

H

HH

H

H

n = 4

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Aromatic HydrocarbonsAromatic Hydrocarbons

• According to Hückel’s criteria, [10]annulene should be aromatic; it has been found, however, that it is not.

• Nonbonded interactions between the two hydrogens that point inward toward the center of the ring force the ring into a nonplanar conformation in which overlap of the ten 2p orbitals is no longer continuous.

[10]Annulene

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Aromatic HydrocarbonsAromatic Hydrocarbons

• What is remarkable relative to [10]annulene is that if the two hydrogens facing inward toward the center of the ring are replaced by a methylene (CH2) group, the ring is able to assume a conformation close enough to planar that it becomes aromatic.

CH2

Bridged [10]annulene

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Antiaromatic HydrocarbonsAntiaromatic Hydrocarbons

Antiaromatic hydrocarbon:Antiaromatic hydrocarbon: A monocyclic, planar, fully conjugated hydrocarbon with 4n pi electrons (4, 8, 12, 16, 20...).• An antiaromatic hydrocarbon is especially unstable

relative to an open-chain fully conjugated hydrocarbon of the same number of carbon atoms.

Cyclobutadiene is antiaromatic.• In the ground-state electron configuration of this

molecule, two electrons fill the 1 bonding MO.

• The remaining two electrons lie in the 2 and 3 nonbonding MOs.

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CyclobutadieneCyclobutadiene

• The ground state of planar cyclobutadiene has two unpaired electrons, which make it highly unstable and reactive.

21-21-2222

CyclooctatetraeneCyclooctatetraene

• Cyclooctatetraene, with 8 pi electrons is not aromatic; it shows reactions typical of alkenes.

• X-ray studies show that the most stable conformation is a nonplanar “tub” conformation.

• Although overlap of 2p orbitals occurs to form pi bonds, there is only minimal overlap between sets of 2p orbitals because they are not parallel.

viewed from above viewed through an edge

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CyclooctatetraeneCyclooctatetraene

MO energy diagram for a planar conformation of cyclooctatetraene.

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Heterocyclic AromaticsHeterocyclic Aromatics

Heterocyclic compound:Heterocyclic compound: A compound that contains more than one kind of atom in a ring. • In organic chemistry, the term refers to a ring with one

or more atoms that differ from carbon.

Pyridine and pyrimidine are heterocyclic analogs of benzene; each is aromatic.

Pyridine

N

N

N••••

Pyrimidine

12

34

5

61

2

3 4

5

6

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PyridinePyridine

• The nitrogen atom of pyridine is sp2

hybridized.• The unshared pair of

electrons lies in an sp2 hybrid orbital and is not a part of the six pi electrons of the aromatic system (the aromatic sextet).

• Resonance energy of pyridine is134 kJ (32 kcal)/mol.

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Furan and PyrroleFuran and Pyrrole

• The oxygen atom of furan is sp2 hybridized.• one unshared pairs of electrons on oxygen lies in an

unhybridized 2p orbital and is a part of the aromatic sextet.

• The other unshared pair lies in an sp2 hybrid orbital and is not a part of the aromatic system.

• The resonance energy of furan is 67 kJ (16 kcal)/mol.

O NH

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Other HeterocyclicsOther Heterocyclics

Purine

Indole

N

N

NN

N

H

H

N

H

CH2CH2NH2

Serotonin(a neurotransmitter)

HO

Caffeine

N

NN

N

O

O

H3CCH3

CH3

21-21-2828

Aromatic Hydrocarbon IonsAromatic Hydrocarbon Ions

Any neutral, monocyclic, unsaturated hydrocarbon with an odd number of carbons must have at least one CH2 group and, therefore, cannot be aromatic.

• Cyclopropene, for example, has the correct number of pi electrons to be aromatic, 4(0) + 2 = 2, but does not have a closed loop of 2p orbitals.

Cyclopropene Cyclopentadiene Cycloheptatriene

CH2 CH2CH2

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Cyclopropenyl CationCyclopropenyl Cation

• If, however, the CH2 group of cyclopropene is transformed into a CH+ group in which carbon is sp2 hybridized and has a vacant 2p orbital, the overlap of orbitals is continuous and the cation is aromatic.

Cyclopropenyl cation represented as a hybrid of three equivalent contributing structures

+

H

H

H

H

H

H

H

H

H+

+

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Cyclopropenyl CationCyclopropenyl Cation

• When 3-chlorocyclopropene is treated with SbCl5, it forms a stable salt.

• This chemical behavior is to be contrasted with that of 5-chloro-1,3-cyclopentadiene, which cannot be made to form a stable salt.

+

Cyclopropenyl hexachloroantimonate

+

3-Chloro-cyclopropene

HH

ClSbCl5 SbCl6

-

Antimony(V) chloride(a Lewis acid)

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Cyclopentadienyl CationCyclopentadienyl Cation

• If planar cyclopentadienyl cation were to exist, it would have 4 pi electrons and be antiaromatic.

• Note that we can draw five equivalent contributing structures for the cyclopentadienyl cation. Yet this cation is not aromatic because it has only 4 pi electrons.

Cyclopentadienyltetrafluoroborate

++

5-Chloro-1,3-cyclopentadiene

H

ClHAgBF4 BF4

- + AgCl

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Cyclopentadienyl Anion, CCyclopentadienyl Anion, C55HH55--

To convert cyclopentadiene to an aromatic ion, it is necessary to convert the CH2 group to a CH group in which carbon becomes sp2 hybridized and has 2 electrons in its unhybridized 2p orbital.

••

• • H

HH

H

H

the origin of the 6 pi electronsin the cyclopentadienyl anion

Cyclopentadienyl anion (aromatic)

HH

HH

H:

H

HH

HH

n = 1

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Cyclopentadienyl Anion, CCyclopentadienyl Anion, C55HH55--

• As seen in the Frost circle, the six pi electrons of cyclopentadienyl anion occupy the 1, 2, and 3 molecular orbitals, all of which are bonding.

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Cyclopentadienyl Anion, CCyclopentadienyl Anion, C55HH55--

The pKa of cyclopentadiene is 16.• In aqueous NaOH, it is in equilibrium with its sodium

salt.

• It is converted completely to its anion by very strong bases such as NaNH2 , NaH, and LDA.

pKa 15.7pKa 16.0

Na+ + H2OH

H

H

H

H

CH2 + NaOH :

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Cycloheptatrienyl Cation, CCycloheptatrienyl Cation, C77HH77++

Cycloheptatriene forms an aromatic cation by conversion of its CH2 group to a CH+ group with its sp2 carbon having a vacant 2p orbital.

+

Cycloheptatrienyl cation (Tropylium ion) (aromatic)

H

HH

H

H

HH

H

HH

H

H

HH

+

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NomenclatureNomenclature

Monosubstituted alkylbenzenes are named as derivatives of benzene.• Many common names are retained.

Toluene CumeneEthylbenzene Styrene

Phenol Aniline Benzoic acid Anisole

COOHNH2 OCH3OH

Benzaldehyde

CHO

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NomenclatureNomenclature

Benzyl and phenyl groups

(Z)-2-Phenyl-2-butene

4-(3-Methoxyphenyl)-2-butanone

1-Phenyl-1-pentanone

O OH3CO

Ph

BenzenePhenyl group, Ph- Toluene Benzyl group, Bn-

CH3 CH2

21-21-3838

Disubstituted BenzenesDisubstituted Benzenes

Locate 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.

CH3

Br

COOHNO2

Cl

NH2

CH3

CH3

2-Nitrobenzoic acid

(o-Nitrobenzoic acid)

3-Chloroaniline(m-Chloroaniline)

4-Bromotoluene(p-Bromotoluene)

m-Xylene

21-21-3939

Disubstituted BenzenesDisubstituted Benzenes

• Where neither group imparts a special name, locate the groups and list them in alphabetical order.

CH2CH3

Cl

NO2Br

1-Bromo-2-nitrobenzene (o-Bromonitrobenzene)

1-Chloro-4-ethylbenzene (p-Chloroethylbenzene)

12

3

4 2

1

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Polysubstituted DerivativesPolysubstituted Derivatives

• 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.

CH3

NO2

OH

Br

Br

NO2

CH2CH3

Br

4

2

1

6

4

21

4

1 2

4-Chloro-2-nitro-toluene

2,4,6-Tribromo-phenol

2-Bromo-1-ethyl-4-nitrobenzene

Br

Cl

21-21-4141

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 OHOHOH

OHCH3

OH

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Acidity of PhenolsAcidity of Phenols

Phenols are significantly more acidic than alcohols.

OH H2O

CH3CH2OH H2O

O-

CH3CH2O-

H3O+

H3O+

pKa = 9.95+

+

+

+ pKa = 15.9

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Acidity of PhenolsAcidity of Phenols

Separation of water-insoluble phenols from water-insoluble alcohols.

21-21-4545

Acidity of Phenols (Resonance)Acidity of Phenols (Resonance)

• The greater acidity of phenols compared with alcohols is due to the greater stability of the phenoxide ion relative to an alkoxide ion.

These 2 Kekuléstructures areequivalent

HH

OO O O

H

O

These three contributing structuresdelocalize the negative chargeonto carbon atoms of the ring

H

OO O O

H

O

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Phenol Subsitituents (Inductive Effect)Phenol Subsitituents (Inductive Effect)

Alkyl and halogen substituents effect acidities by inductive effects:• Alkyl groups are electron-releasing.• Halogens are electron-withdrawing.

p-ChororophenolpKa 9.18

m-ChlorophenolpKa 8.85

PhenolpKa 9.95

m-CresolpKa 10.01

p-CresolpKa 10.17

OH OH OH OH OH

CH3

CH3

ClCl

21-21-4747

Phenol Subsitituents(Resonance, Inductiion)Phenol Subsitituents(Resonance, Inductiion)

• Nitro groups increase the acidity of phenols by both an electron-withdrawing inductive effect and a resonance effect.

OH

NO2

OH OH

NO2PhenolpKa 9.95

p-NitrophenolpKa 7.15

m-NitrophenolpKa 8.28

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Acidity of PhenolsAcidity of Phenols

• Part of the acid-strengthening effect of -NO2 is due to its electron-withdrawing inductive effect.

• In addition, -NO2 substituents in the ortho and para positions help to delocalize the negative charge.

+ +

delocalization of negativecharge onto oxygen furtherincreases the resonancestabilization of phenoxide ion

O

O O

NO

O

NO

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SynthesisSynthesis: Alkyl-Aryl Ethers: Alkyl-Aryl Ethers

Alkyl-aryl ethers can be prepared by the Williamson ether synthesis:• but only using phenoxide salts and haloalkanes.• haloarenes cannot be used because they are

unreactive to SN2 reactions.

no reaction+X RO-Na

+

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SynthesisSynthesis: Alkyl-Aryl Ethers: Alkyl-Aryl Ethers

OH CH2=CHCH2ClNaOH, H2O, CH2Cl2

OCH2CH=CH2

Phenyl 2-propenyl ether(Allyl phenyl ether)

+

Phenol 3-Chloropropene(Allyl chloride)

OH

O

O

CH3OSOCH3NaOH, H2O, CH2Cl2

OCH3 Na2SO4+

Methyl phenyl ether(Anisole)

+

Phenol Dimethyl sulfate

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SynthesisSynthesis: Kolbe Carboxylation: Kolbe Carboxylation

Phenoxide ions react with carbon dioxide to give a carboxylate salt.

OH

NaOHH2O

O-Na

+

CO2

H2O

OHCO

-Na

+O

HClH2O

OH O

COH

Phenol Sodiumphenoxide

Sodium salicylate Salicylic acid

21-21-5454

Mechanism: Mechanism: Kolbe CarboxylationKolbe Carboxylation

• The mechanism begins by nucleophilic addition of the phenoxide ion to a carbonyl group of CO2.

O

C

O

O

OC

H

OO OH

CO

O

A cyclohexadienoneintermediate

+

Sodium phenoxide

Salicylate anion

keto-enoltautomerism

(1) (2)

Go back to aromatic structure

21-21-5555

Synthesis: Synthesis: QuinonesQuinones

Because of the presence of the electron-donating -OH group, phenols are susceptible to oxidation by a variety of strong oxidizing agents.

H2 CrO4

Phenol 1,4-Benzoquinone(p-Quinone)

O

O

OH

21-21-5656

QuinonesQuinones

OHOH K2Cr2O7

OH

OH

H2SO4

K2Cr2O7

H2SO4

O

O

OO

1,4-Benzoquinone (p-Quinone)

1,2-Benzenediol (Catechol)

1,2-Benzoquinone (o-Quinone)

1,4-Benzenediol(Hydroquinone)

21-21-5757

QuinonesQuinones

Readily reduced to hydroquinones.

1,4-Benzoquinone(p-Quinone)

(reduction)

1,4-Benzenediol(Hydroquinone)

O

O

OH

OH

Na2S2O4, H2O

21-21-5858

Coenzyme QCoenzyme Q

Coenzyme Q is a carrier of electrons in the respiratory chain.

O

O

MeO

HMeO MeO

MeO

OH

OH

Hn n

Coenzyme Q(oxidized form)

Coenzyme Q(reduced form)

reduction

oxidation

21-21-6060

Benzylic OxidationBenzylic Oxidation

Benzene is unaffected by strong oxidizing agents such as H2CrO4 and KMnO4

• Halogen and nitro substituents are also unaffected by these reagents.

• An alkyl group with at least one hydrogen on its benzylic carbon is oxidized to a carboxyl group.

2-Chloro-4-nitrotoluene 2-Chloro-4-nitrobenzoic acid

H2CrO4

O2N Cl

CH3

O2N Cl

COOH

21-21-6161

Benzylic OxidationBenzylic Oxidation

• If there is more than one alkyl group on the benzene ring, each is oxidized to a -COOH group.

1,4-Dimethylbenzene (p-xylene)

1,4-Benzenedicarboxylic acid (terephthalic acid)

CH3 H2 SO4

K2Cr2O7H3C COH

O

HOCO

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Benzylic ChlorinationBenzylic Chlorination

Chlorination and bromination occur by a radical chain mechanism.

CH3

Cl2+

CH2Cl

HCl+

Toluene

heat or light

Benzyl chloride

(PhCO2)2, CCl4

NBS

Br

Ethylbenzene 1-Bromo-1-phenylethane(racemic)

21-21-6363

Mechanism: Mechanism: Benzylic ReactionsBenzylic Reactions

Benzylic radicals (and cations also) are easily formed because of the resonance stabilization of these intermediates.• The benzyl radical is a hybrid of five contributing

structures.

C

C

C

C C

21-21-6464

Benzylic HalogenationBenzylic Halogenation

• Benzylic bromination is highly regioselective.

• Benzylic chlorination is less regioselective.

(PhCO2)2, CCl4

NBS

Br

Ethylbenzene 1-Bromo-1-phenylethane(the only product formed)

Cl

Cl2 +

heat or light

1-Chloro-2-phenylethane

(10%)

Ethylbenzene

+

1-Chloro-1-phenylethane

(90%)

Cl

21-21-6565

HydrogenolysisHydrogenolysis

Hydrogenolysis:Hydrogenolysis: Cleavage of a single bond by H2

• Benzylic ethers are unique in that they are cleaved under conditions of catalytic hydrogenation.

O H2Pd/C

OHMe

+

Benzyl butyl ether Toluene1-Butanol

+

this bondis cleaved

21-21-6666

Synthesis, Protecting Group: Synthesis, Protecting Group: Benzyl EthersBenzyl Ethers

The value of benzyl ethers is as protecting groups for the OH groups of alcohols and phenols.• To carry out hydroboration/oxidation of this alkene,

the phenolic -OH must first be protected; it is acidic enough to react with BH3 and destroy the reagent.

OH

1. ClCH2Ph

O Ph

2. BH3•THF

Et3N 3. H2O2/NaOH

H2

Pd/CO Ph

OH

OH

OH

2-(3-Hydroxypropyl)phenol

2-(2-Propenyl)phenol(2-Allylphenol)