Chapter 6 Arenes and Aromaticity6.1 The Structure of Benzene 1. A resonance theory 2. An orbital hybridization view 3. The molecular obitals6.2 Nomenclature of Benzene Derivatives6.3 Aromaticity and the Huckel(4n + 2)rule 6.3.1 Annulenes( 轮烯 ) 6.3.2 Aromatic ions 6.3.3 Polycyclic aromatic hydrocarbons6.4 Reactions of Arenes 6.4.1 Aromatic ring as a substituent 1. Halogenation of α - H of arenes

2. Oxidation of Alkylbenzenes 3. Addition Reaction of Alkenylbenzenes6.4.2 Aromatic Ring as a Functional Group: Electrophilic Aromatic Substitution6.4.3 Halogenation of Benzene6.4.4 Nitration of Benzene6.4.5 Sulfonation of Benzene6.4.6 Friedel-Crafts Alkylation of Benzene6.4.7 Friedel-Crafts Acylation of Benzene Clemmensen reduction Wolff-Kishner reduction

6.4.8 Effects of Substituents on Reactivity and Orientation 6.4.8.1 Classification of Substituents 6.4.8.2 Substituent Effects in Electrophilic Aromatic Substitution6.4.9 Multiple Substituent Effects6.4.10 Synthetic Applications

Organic compoundsAliphatic

Aromatic

脂肪族芳香族

Aromatic compound: Benzene

C6H6

Fragrant:

A low ratio hydrogen / carbon.

Balsams( 香脂 )

C

O

H

Benzaldehyde

oil of bitteralmond

COOH

Benzoic acid

CH3

TolueneTolu balsam

Estrone 雌激素酮

CH3CHCH2

CH3

CHCOOH

CH3Ibuprofen 布洛芬

6.1 Structure of BenzeneThree modern theories:1. A resonance theory( 共振论 )1. A resonance theory( 共振论 )

The structure of benzene is planar: regular hexagon( 正六边型 ).The bond angles: 120 °The C–C bond lengths : 1.39Åsp2–sp2 single bond: 1.46Åsp2–sp2 double bond: 1.34A hybrid of the two Kekulé structures:

is equivalent to

Cyclic conjugation in benzene leads to a great stability.

P153,5.3P153,5.3

C C

CCCC HH

H H

2. An orbital hybridization view2. An orbital hybridization view In a mole. of benzene, all C atoms aresp2–hybridized.6 C–C σ bonds: sp2–sp2 overlap,6 C –H σ bonds: sp2–1s overlap.

The 6 2p orbitals thatare perpendicular to the σ frameworkoverlap to form πorbital.

The 6 π electrons aredelocalized over all six C.

Resonanceenergy:152 kJ/mol

Resonanceenergy:152 kJ/mol

A closed π conjugate system.

3. The molecular obitals3. The molecular obitals The 6 overlapping 2p obitals combine to form a set of 6 π molecular orbitals:

Antibonding orbitals

Bonding orbitals

6.2 Nomenclature of Benzene Derivatives 1. Monosubstituted benzenes A. Benzene as the parent name.

CH3

Toluene( 甲苯 )

Cl

Chlorobenzene( 氯苯 ) Isopropylbenzene

CHCH3

CH3

NO2

Nitrobenzene( 硝基苯 )

B. Benzene as a substituentC6H5–, Ph–: phenyl.

PhC CH

Phenylacetylene( 苯乙炔 )

PhC

CH3

CHCH3

2-Phenyl-2-butene

CH2

Diphenylmethane

CH2 Cl

Benzylchloride( 苄基氯 )

P154,5.4P154,5.4

2. Disubstituted benzenesThree isomers:

1,2-Dibromobenzeneo-Dibromobenzene

ortho-

Br

Br

Br

Br1,3-m-

meta-

Br

Br1,4-p-

para-CH3CH3

o-Xylene(0- 二甲 苯 )

3. Polysubstituted Benzenes

2-Chloro-1,4-dinitrobezene

ClNO2

NO2

(1,4- 二硝基 -2- 氯苯 )

CH3

CH3H3C

1,3,5-Trimethylbezene( 均三甲苯 )

Common name:P155

Common name:P155

6.3 Aromaticity and the Huckel (4n + 2) rule

Aromaticity: a special stability.On the basis of the calculation by MO. Theory,

Huckel (4n + 2) rule:a. The monocyclic and fully conjugated polyenes.

Ch.276 Ch.276

b. All atoms in the ring are coplanar.c. The Mole. possesses(4 n+2) π electrons.

6.3.1 Annulenes( 轮烯 )

cyclobutadieneπ electrons 4

[4]-Annulene[6]-Annulene

cyclooctatetraene[8]-Annulene

Tub-mole.

Eric Hückel

1896

"Eric Hückel received his PhD in experimental Physics in 1921 at the University of Göttingen. After spending a year with David Hilbert in mathematics and Max Born, he left Göttingen for a position at the ETH Federal Institute of Technology in Zurich with Peter Debye. While at Zurich, Hückel and Debye developed the Debye-Hückel theory of strongelectrolytes. In 1930 Hückel received an appointment in chemical physics at the Technical Institute in Stuttgart. In 1937 he was appointed a professor of theoreticalphysics at the University of Marburg, where he remained until his retirement in 1962." (Source: DA McQuarrie "Quantum Chemistry", University Science Books, 1983) In the quantum chemistry community, Hückel is best known for introducing in 1930a simple theory for the treatment of conjugated molecules and aromatic molecules.This theory came to be known as"Hückel molecularorbital theory" or simply"Hückel Theory". This was later extended by Roald Hoffmannand has been widely used in organic and inorganic chemistry.

HH

Cyclodecapentaene( 环癸五烯 )

6.3.2 Aromatic ions

H Hstrongbase

H CH2: sp3 sp2cyclopentadieneCyclopentadienyl

anion π electrons: 6

H HCycloheptatriene

( 环庚三 烯 )Cycloheptatrienyl

cation

H

H Ch.P278Ch.P278

6.3.3 Polycyclic aromatic hydrocarbonsP279P279

Naphthalene( 萘 )

Anthracene( 蒽 )

Phenanthrene( 菲 )

12

345

6

78 1

2

345

6

78 9

10 56

7

1

2

34

8

9 10

The hybrid of three resonance forms

• following Hückel rule• Aromaticity

6.4 Reactions of Arenes6.4.1 Aromatic ring as a substituent

CH3Cl2h

CH2ClCl2h

CHCl2Cl2h

CCl3Ex.

1. Halogenation of α - H of arenes

CH2CH3 + N

O

O

Br PhCOOCPh

O O

CCl4, 80 C°CHCH3

Br

+ N

O

O

H

Ethylbenzene N-BromosuccinimideN- 溴代丁二酰亚胺

(NBS)

(87%)

Allylic halogenation:Allylic halogenation:CH3 CH CH2

NBSh,CCl4

CH2 CH CH2

Br

2. Oxidation of Alkylbenzenes P170,5.11P170,5.11

The alkyl side chain with α - H on a benzene ring is oxidized to benzoic acid by chromic acid( 铬酸 ) or KMnO4:

(86%)

t-Butylbenzene

CH2CH2RNa2Cr2O4

H2O,H2SO4,heatCOOH

CH3

NO2

Na2Cr2O4

H2O,H2SO4,heat

COOH

NO2

C

CH3

CH3CH3

Na2Cr2O4

H2O,H2SO4,heatNO reaction

Oxidant:KMnO4

3. Addition Reaction of Alkenylbenzenes6.4.2 Aromatic Ring as a Functional Group: Electrophilic Aromatic Substitution

( 芳环上的亲电取代反应 ) P157 P157

When the aromatic ring of benzene reacts with a electrophilic reagent, the substitutionreaction occurs: A benzene ring with

6 π electrons in a cyclic conju-gated system is a site of electron-rich.

+ E Y

+ YHE

+ E Y

+ YHE

Electron donor: benzene ringElectron acceptor: E+, a Lewisacid.

Aromatic electrophilic substitution reactions: The electrophlic part of a reagent replaces a hydrogen atom from aromaticring.

Figure 1 Types of electrophilic aromatic substitution of benzeneFigure 1 Types of electrophilic aromatic substitution of benzene

HHalogenationHalogenation

NO2

NitrationNitration SO3H

SulfonationSulfonation

R

AlkylationAlkylation

Acylation( 酰基化 )

Acylation( 酰基化 )

C

O

RXP157P157

H+ Br2

Feheat

Br+ HBr

(75%)The Lewis acids most commonly used are FeCl3, FeBr3 and AlCl3.

2Fe + 3X2 2FeX3

The mechanism for bromination of benzene:Step 1 Polarization of Br2.

Br Br + FeBr3 Br FeBr3

BrBr Br + FeBr3 Br FeBr3

Br

The formation of the bromine-iron(III)bromide complex.

6.4.3 Halogenation of Benzene

Step 2 The attack of polarized bromine to benzene ring .

+ Br FeBr3

Br

BrH + Br FeBr3

slow

The formation of nonaromatic carbocation.Allylic cation: p- π conjugation

Delocalization of π - electrons generatesthe resonance forms:

BrH

BrH

BrH

BrH

BrH

BrH

Step 2 is rate-determining.Step 3 The loss of a proton to restore the aromatic system.

BrH + Br FeBr3

Br+ FeBr3HBr +

Step 1. Polarization of Br2.

Step 2 The attack of polarized bromine to benzene ring .

Step 3 The loss of a proton to restore the aromatic system.

Reactivity : F2 > Cl2 > Br2 > I2 Iodination has to carry out in the presence of an oxidizing agent:

+ I2HNO3

I

Iodobenzene(86%)Ex.

6.4.4 Nitration( 硝化反应 ) of Benzene Aromatic rings can be nitrated by reaction with a mixture of concentratednitric acid and sulfuric acid:

+ HNO3H2SO4

50 - 55 C°

NO2+ H3O + HSO4

The generation of electrophile, E+:HNO3 + 2H2SO4 NO2 + H3O + 2HSO4

Nitronium ion( 硝 离子 )

Nitrobenzene(85%)

CH3NO2

NO2

O2N

Trinitrotoluene(TNT)

6.4.5 Sulfonation( 磺化反应 ) of Benzene Benzene reacts with fuming sulfuric acid to produce benzene sulfonic acid:

H+ S

O

OO

25 C°

concd H2SO4

S

O

O

OH

Sulfur trioxide Benzenesulfonic acid ( 苯磺酸 )(56%)

Fuming H2SO4: a mixture of H2SO4 and SO3.

Mechanism of the reaction:

Step 1 Generation of the electrophile:

2H2SO4 SO3 + H3O + 2HSO4

Step 2. Sulfur trioxide as a electrophile attacks benzene in the rate-determing step.

Step 3. The loss of a proton to restore the aromatic system.

Step 4. A rapid proton transfer to produce benzenesulfonic acid.

Sulfonation is favored in strong acid,Desulfonaton is favored in hot,dilute aqueous acid.

The sulfonation of benzene is reversible.The sulfonation of benzene is reversible.

SO3+ H2SO4

fastSO3H

HSO4+

H2N

SO O

NH2

Sulfanilamide( 磺胺 )SO3

H + HSO4fast SO3

+ H2SO4

H+ S

O

OO

slow SO3H An antibiotic

6.4.6 Friedel-Crafts Alkylation of Benzene Benzene reacts with alkyl halide in the presence of AlCl3 as catalyst:

+ CH3CHCH3

Cl

AlCl3 CHCH3

CH3+ HCl

Cumene( 枯烯 )IsopropylbenzeneMechanism of the reaction:

Step 1. The formation of carbocation:

CH3

CHCH3

Cl + AlCl3CH3

CHCH3

+ Cl AlCl3

Step 2. The carbocation as a electrophile attacks benzene ring, a C–C bond is formed:

H+

CH3

CH

CH3

slow CHCH3H

CH3

CHCH3H

CH3

+ Cl AlCl3fast CHCH3

CH3

+ HCl + AlCl3

• CH3X and RCH2X do not form the carbocation, they form the complex:

RCH2 X AlX3

• The rearrangement can occur when especially a primary halides are used:

H+ (CH3)2CHCH2Cl

AlCl30 C°

C(CH3)3 + HCl

(66%)

Step 3. Loss of a proton to produce the alkylbenzene

CCH3

CH3

CH2

H

Cl AlCl3 CCH3

CH3

CH3 + Cl AlCl3

• Friedel-Crafts alkylation can be availble to other systems that generate a carbocation:Ex.

A alkene and a acid.

A alcohol and a acid. (56%)

+H2SO4

+ HOBF3

60 C°

Cyclohexyl benzene(65%)

• Polyalkylation

Ch. P252 Ch. P252

+ (CH3)3CClAlCl3

C(CH3)3

+

C(CH3)3

C(CH3)3

+

Majorproduct

Minorproduct

Another limitation to alkylation on ring

Charles Friedel (1832-1899) Charles Friedel was born inStrabourg, Frans,and studiedat the Sorbonne in Paris. He was among the first to attempt manufacture synthetic diamonds. He was professor of chemistry at the Sorbonne(1884-1889).

James Mason Crafts (1839-1917)James Mason Crafts was born in Boston, Massachusetts,and graduated from Harvard in 1858. He served as president in the Massachusetts Institute ofTechnology (1897-1900).

6.4.7 Friedel-Crafts Acylation of Benzene ( 酰基化反应 ) Benzene reacts with a acyl halide ( 酰卤 ) in the presence of AlCl3, to produce a acylbenzene( 酰基苯 ).

H+ CH3C

O

ClAlCl3

80 C°excess benzene

CCH3

O

+ HCl

Acetophenone( 苯乙酮 )(97%)Reagents: Acyl chloride (or acid chloride):

80 C°CH3C

O

OH SOCl2+ CH3C

O

Cl + SO2 + HCl

Carboxylic acids react with thionyl chloride( 亚硫酰氯 ) or PCl5:

Carboxylic acid anhydrides( 酸酐 ):H

+ CH3C

O

O CCH3

OAlCl3

excess benzeneCCH3

O

+ CH3C

80 C°

O

OH

(83%)

Ch. P252Ch. P252

• Limitation to Friedel-Crafts Reactions:• Limitation to Friedel-Crafts Reactions:Friedel-Crafts reactions do not occur when powerful electron-drawing groupsare present on the aromatic ring.

-NO2, -SO3H, RCO-,-COOH, -NR3 ect..+

AlCl3

NH2

+ R X NO reaction

NH2 + AlCl3 NH2 AlCl3

Preparation of unbranched alkyl benzene:

+ CH3CH2CH2CCl

OAlCl3 CCH2CH2CH3

O

+ HCl

• Application of acylation to aromatic ring• Application of acylation to aromatic ring

1-Pheny-1-butanone(1- 苯基 1- 丁酮 )(86%)

Clemmensen reduction:Clemmensen reduction:

The ketone can be reduced to alkylbenzeneby refluxing with HCl containing amalgamated zinc( 锌汞齐 ):

C

OCH2

CCH2CH2CH3

OHCl

Zn(Hg)CH2CH2CH2CH3

Butylbenzene(73%)

Wolff-Kishner reduction:Wolff-Kishner reduction:Heating with hydrazine( 肼 ) and hydroxide

CCH2CH3

OH2NNH2,KOHtriethylene glycol

175 C°

CH2CH2CH3

1-Pheny-1-propanone(1- 苯基 -1- 丙酮 )

Propylbezene( 丙苯 )(82%)

HOCH2CH2OCH2CH2OCH2CH2OHTriethylene glycol( 三甘醇 or 三 缩 乙二醇 )

Ch.P355Ch.P355

6.4.8 Effects of Substituents on Reactivity and Orientation

P164, 5.9P164, 5.9Y

To substituted benzenes: the substituent on the ring affects both the rate of the reaction and the site of attack.

Effect of substituents on the reactivity and orientation or regioselectivity.

Substituents can be classified into three groups:

1. Ortho and para Directing activators1. Ortho and para Directing activators（邻、对定位致活基团）

Substituents in first category( 第一类定位基团 )• Making the ring more reactive than benzene.

6.4.8.1 Classification of Substituents

Hydroxyl groupis a activitor Hydroxyl groupis a activitor

OH H Cl NO2OH H Cl NO2

Relative rateof nitration 1000 1 0.033 6 × 10-8

Reactivity • Directing substitution primarily to the ortho and para position to themselves

CH3

HNO3

HOAc

CH3

NO2+

CH3

+

CH3

NO2

NO2

o- p- m-63% 34% 3%

2. Meta directing deactivators

• Making the ring less reactive than benzene.

( 间位定位致钝基团 )Substituents in second category( 第二类定位基团 )

Ex. –NO2, –CF3 etc.(et cetera[it´setr ])e

• Directing substitution primarily to the meta position to themselves

CF3

HNO3

H2SO4

CF3

NO2+

CF3

+

CF3

NO2

NO2

6% 3% 91%

3. Ortho and para directing deactivators3. Ortho and para directing deactivators

–X: ClHNO3

H2SO4

ClNO2

+

Cl

+

Cl

NO2

NO2

30% 69% 1%

X –I, +C

Ortho- andpara- directing

activitors

Ortho- andpara- directing

deactivitors

Meta-directing

deactivitors

FIGURE 6.1 Classification of substituent effects in electrophilic aromatic substitution.

OCH3 CH3NHCOCH3 Cl I C OR

OH(R)C C OH

O OSO3H C N

NH2 F Br NO2OH HO CF3 CCl3 NR3

6.4.8.2 Substituent Effects in electrophilic Aromatic substitution

Substituent Effects

P166P166

Meta-directingdeactivitors

Electron-withdrawing

Ortho- and para- directingactivitors

Electron-releasing

Reactivity

1. Ortho and para directing activitorsActiviting effect:

CH3CH3

E

E

H

• Electron-releasing groups increase the density of electron cloud to favor electrophilic attack.

• stabilize the carbocation.Orientation effect:

OH

EH

EH

EH

OH OH OHEH

OH

Orthoattack

Paraattack

OH

EH

OH

EH

OH

EH

Metaattack

Most stableresonancestructure

Most stableresonancestructure

OH

E H

OH

E H

OH

E H

OH

HE

Para and orthoattacks are primary.

Para and orthoattacks are primary.

P168, P168,

2. Meta directing deactivitorsDeactiviting effect:

CF3

E

CF3

EH

• Electron-drawing groups decrease the density of electron cloud of aromatic ring.• Making intermedias highly unstable

Orientation effect:

CF3

CF3EH

EH

EH

CF3 CF3

Orthoattack

EH

EH

EH

CF3 CF3 CF3

Paraattack

Metaattack

Most unstableintermeidate

Meta attack is primary

Meta attack is primary

E H E H HE

CF3 CF3 CF3

3. HalogensX Halogen as a substituent on aromatic ring

possesses both electron-drawing inductiveeffect(-I) and electron-releasing conjugativeeffect(+C).

X -I > +C

OROH

NH2

-I < +C

Inductive effect of halo-groupdeactivates aromatic ring.

Halo-group stabilizes the inter-mediate relative to that from ortho and para attack deactivates aromatic ring by donating unshared pair of electrons in the same way as –OH.

Cl

E H

Cl

E H

Cl

E H

Cl

HE

Ch.P262Ch.P262

6.4.9 Multiple Substituent Effects X

Y

Further electrophilic substitution of a disubstituted bezene is governed by Additivity( 累加性 ) of effects.

1. If the directing effects of the two groups reinforce( 增强 ) each other, there is no problem.

CH3

NO2

HNO3H2SO4

CH3

NO2

NO2

2. If the directing effects of the two groups are oppose each other, the more powerful activiting group has the dominant influence.

Ch. P266Ch. P266

NHCH3

Cl

Br2HOAc

NHCH3

Cl

Br

CH3

COOHH2SO4

HNO3

CH3

COOHNO2

+

CH3

COOH

O2N

3. When two positions are comparably actived by alkyl group, substitution usually occurs at the less hindered site.

(88%)

CH3

CHCH3 CH3

HNO3

CH3

CHCH3 CH3

NO2

H2SO4

6.4.10 Synthetic ApplicationsCh.172,5.13Ch.172,5.13Ex. 1

4-Chloro-1-nitro-2-propylbenzene(2- 丙基 -4- 氯硝基苯 )

NO2

Cl CH2CH2CH3

Cl

NO2

Cl

NO2

NO2 NO2

ClCl

m-ChloropropiophenoneSynthetic route:( 间 - 氯苯基乙基 ( 甲 ) 酮

( )

( )( )

Cl

NO2

( )( )

( )

O

( )( )

( )( )

CH3CH2CCl

O

AlCl3

OCl

Cl2

FeCl3

ClH2NNH2

KOHHNO3

H2SO4

Retrosynthetic analysisRetrosynthetic analysisO

Cl

P178, 5.22 (a), (c)5.23 (c), (f)5.26 (b)5.275.28 (b) ( 苯基腈 或氰基苯 )5.32 (b) ( 邻 - 甲基苯酚 )5.33 (c)5.395.40 (b)5.41(b)5.425.445.45

P178, 5.22 (a), (c)5.23 (c), (f)5.26 (b)5.275.28 (b) ( 苯基腈 或氰基苯 )5.32 (b) ( 邻 - 甲基苯酚 )5.33 (c)5.395.40 (b)5.41(b)5.425.445.45

5.485.495.505.51

5.485.495.505.51

Chapter 6 to Problems