Chapter 9 Aromatic compounds

芳香化合物

Text 1: chapter 16, 17

Text 2: 第七章

Contents 1. The structure of benzene 2. Aromaticity 3. Nomenclature of benzene derivatives 4. Physical properties 5. Reactions of benzene and its derivatives Electrophilic aromatic substitution ----Effects of s

ubstituents: Reactivity and orientation Nucleophilic aromatic substitution Addition reactions of benzene derivatives Side-chain reactions of benzene derivatives Reactions of phenols

Discovery of Benzene

• Isolated in 1825 by Michael Faraday who determined C:H ratio to be 1:1.

• Synthesized in 1834 by Eilhard Mitscherlich who determined molecular formula to be C6H6.

• Other related compounds with low C:H ratios had a pleasant smell, so they were classified as aromatic( 芳香性的 ).

The Kekule Structure for benzene 苯的克库勒结构

1. The Structure of benzene (16-2, 3)

　 Proposed in 1866 by Friedrich Kekulé, shortly after multiple bonds were suggested.

　 Failed to explain existence of only one isomer of 1,2-dichlorobenzene.

orC

CC

C

CC H

H

H

H

H

H

Cl

Cl

Cl

Cl

Same compund

Modern theories of the structure of benzene

RT

Antibonding MO

Bonding MO

·´ ¼ü¹ì µÀ

³É¼ü¹ì µÀ

VB

MO

Hydrogenation of just one double bond in benzene is endothermic （吸热） !

The unusual stability of benzene

Differences in Reactions between alkene and benzene

Br2 / CCl4dark, 25oC

KMnO4 / H2O

25 oC

H2O, HClheat

H2 / Ni

No addition

No hydration

No oxidation

Slow additionat hight temperatureand pressure

Br2 FeBr3

Br

Aromatic Requirements

• Structure must be cyclic with conjugated pi bonds.

• Each atom in the ring must have an unhybridized p orbital.

• The p orbitals must overlap continuously around the ring. (Usually planar structure)

• Compound is more stable than its open-chain counterpart

2. Aromaticity 芳香性

Anti- and Nonaromatic反芳香性和非芳香性

• Antiaromatic （反芳香性的） compounds are cyclic, conjugated, with overlapping p orbitals around the ring, but the energy of the compound is greater than its open-chain counterpart.

• Nonaromatic （非芳香性的） compounds do not have a continuous ring of overlapping p orbitals and may be nonplanar.

Hückel’s Rule （休克尔规则）

• If the compound has a continuous ring of overlapping p orbitals and has 4N + 2 pi 　 electrons, it is aromatic.

• If the compound has a continuous ring of overlapping p orbitals and has 4N electrons, it is antiaromatic.

The (4n+2) pi-Electron Rule

(1) polynuclear aromatic hydrocarbons (PAH, 多核芳烃 ,16-10)

7

8

9

1012

3

4

Phenanthrene·Æ

6

5

2 5

4

10

6

3

78

PyreneÜÅ

1

9

Other aromatic compounds

NaphthaleneÝÁ

12

3

456

78

AnthraceneÝì

12

3

45

6

78 9

10

Fused aromatic compounds 稠环芳烃

As the number of aromatic rings increases, the resonance energy per ring decreases, so larger PAH’s will add Br2.

(mixture of cis and trans isomers)

H Br

H BrH BrH

Br

• [4]Annulene is antiaromatic (4N e-’s)• [8]Annulene would be antiaromatic, but it’s no

t planar, so it’s nonaromatic.• [10]Annulene is aromatic except for the isome

rs that are not planar.• Larger 4N annulenes are not antiaromatic bec

ause they are flexible enough to become nonplanar.

(2) [N]annulenes ( 轮烯 )

HH[10]annulene

nonaromatic

[8]annulene Nonaromatic非芳香性

[18]annulene Aromatic if planar

[16]annulene Antiaromatic if planar

H HHH[14]annulene

nonaromatic

O O

A B

Problem: Which molecule is more stable?

Azulene 奥

(aromatic)

The dipole moment is 1.0D( aromatic 具有芳香性 )

H3C CH3

Answer: (A)

MO Derivation of Hückel’s Rule

• Lowest energy MO has 2 electrons.• Each filled shell has 4 electrons.

=>

The Polygon Rule 多边形规则

ring

Number of πelectrons

π*

π*

nE

Cyclopentadienyl Ions 环戊二烯离子

4 electrons, antiaromatic. 6 electrons, aromatic.

H H

+ OC(CH3)3

H

+ HOC(CH3)3

pKa = 16 pKa = 19

Acidity

Aromatic ions

Tropylium Ion 卓翁离子

6 p electrons and an empty p orbital.

Aromatic: more stable than open chain ion

Cycloheptatrienyl cation环庚三烯阳离子

H OHH+, H2O

H H

Aromatic ions

Dianion of [8]Annulene [8] 轮烯二价阴离子

10 p electrons, aromatic.

Cyclooctatetraenyl dianion环辛四烯二价阴离子

+ 2K + 2K+

Aromatic ions

(3) Heterocyclic aromatic compounds （ 16-9 ） 杂环芳香化合物（中文下册）

N

pyridine吡啶

NH

pyrrole吡咯

O

furan呋喃

S

thiophene噻吩

Pyridine 吡啶

Nonbonding pair of electrons in sp2 orbital, so weak base, pKb = 8.8.

N

Pyrrole 吡咯

Also aromatic, but lone pair of electrons is delocalized, so much weaker base.

NH

Basic or Nonbasic?

NNPyrimidine （嘧啶） has two basicnitrogens.

N N H Imidazole （咪唑） has one basicnitrogen and one nonbasic.

N

N

N

N

H

Purine （嘌呤） ?

=>

3. Nomenclature of benzene derivatives

(1) Monosubstituted benzenes

“XXbenzene” ， XX 苯

Fluorobenzene( 氟苯）

Chlorobenzene（氯苯）

Bromobenzene（溴苯）

Nitrobenzene( 硝基苯）

F Cl Br NO2

SO3H COOH COCH3 OCH3

Benzenesulfonic acid苯磺酸

Benzoic acid苯甲酸

Acetophenone苯乙酮

Anisole苯甲醚

CH3 CH2CH3 OH NH2

MethylbenzeneToluene( 甲苯）

Ethylbenzene（乙苯）

HydroxybenzenePhenol（苯酚）

AminobenzeneAniline（氨基苯， 苯胺）

Br BrBr

Br

BrBr

1,3-Dibromobenzenem-Dibromobenzene间二溴苯

1,2-Dibromobenzeneo-Dibromobenzene 邻二溴苯

1,4-Dibromobenzenep-Dibromobenzene对二溴苯

(2) disubstituted benzenes 1,2-; 1,3-; 1,4- o- ( 邻 ), m- ( 间 ), p- ( 对 )

CH3 CH3

CH3

CH3

CH3

CH3

1,2-Dimethylbenzene 1,3-Dimethylbenzne 1,4-Dimethylbenzeneo-xylene 　 m-xylene p-xylene

COOH COOHCOOH

NO2

NO2NO2

2-Nitrobenzoic acid 3-Nitrobenzic acid 4-Nitrobenzic acid

o-Nitrobenzoic acid m-Nitrobenzoic acid p-Nitrobenzoic acid

CH2

Benzyl

CH2Cl

Benzyl chlorideÜлùÂÈÜлù

(3) benzene as substituent: phenyl group ( 苯基 ) ， Ph-

CH2CH2CH2CH3 CH3C=CHCH3

Ph

CH3CHCH2CH2CH2CH2CH3

Ph

Butylbenzene 2-Phenyl-2-butene 2-Phenylheptane

Benzyl group ( 苄基 ),Bn-

Aryl group ( 芳基 ),Ar- Arene = Aromatic hydrocarbon

• Melting points: More symmetrical than corresponding alkane, pack better into crystals, so higher melting points.

• Boiling points: Dependent on dipole moment, so ortho > meta > para, for disubstituted benzenes.

• Density: More dense than nonaromatics, less dense than water.

• Solubility: Generally insoluble in water.

4. Physical properties and spectroscopy of aromatic compounds

UV: 254 nm (B 带 )

IR: 3030 (C-H), 1600 (skeleton), 1500 cm-1

1H NMR: 7~9ppm

MS:

m/z, 91

CH2+

+

m/z, 65

+

spectroscopy of aromatic compounds

O

1-phenylpropan-2-one

M+, 134 m/z, 119 m/z, 91

CCH3

O

CO

CH2

m/z, 65

Assignments: T-1: 16-27, 28, 30, 33, 36

Chapter 9 Aromatic compounds

5. Reactions of benzene and its derivatives

(Chapter 17)

Chapter 9 Aromatic compounds

Many benzene and naphthalene( 萘 ) derivatives are useful drugs

阿司匹林，消炎止痛

布洛芬，止痛 沙丁胺醇，

哮喘

对乙酰氨基酚，扑热息痛

萘普生，关节炎 普鲁卡因，

局部麻醉

芬氟拉明，减肥

1) Electrophilic aromatic substitution reactions

17-2

17-3

17-4

17-10

17-11

X2, FeX3

(X = Cl, Br)

X+ HX

Halogenation±»¯

NO2HNO3

H2SO4 + H2O

SO3

H2SO4

SO3H

RCl, AlCl3 R+ HCl

RCOCl, AlCl3 R

O

Nitration Ïõ »¯

Sulfonation»Ç»¯

Friedel-Crafts Alkylation傅-¿ËÍé »ù»¯

Friedel-Crafts Acylation傅-¿Ëõ£»ù»¯+ HCl

Electrophilic addition-elimination mechanism亲电加成 - 消除机理

Arenium ion ( 芳基正离子 ) intermediateσ- complex (σ- 络合物）

+ E+

E

H

+ E

H+

E

H+

Step 1: addition

Step 2: elimination

E

H

+

+ H+

E

E

H+

Eact1

Eact2

TS 1

TS 2

E

reaction coordination

The reaction-energy diagram ( 反应能线图 )

rate-limiting step

reactants

σ-complex

product

Halogenation of benzene: X2, FeX3

Reactivity: F2 > Cl2 > Br2 > I2

Br Br FeBr3

+ BrH

+ Br

H+

Br

H++ FeBr4

Br Br + FeBr3 Br Br FeBr3

+

+ I2I

HNO3

86%

+ + NO2 + H2O

BrH

+ Br

+ H[FeBr4]

FeBr4FeBr3 + HBr

I2 + 2HNO3 + 2H+ 2I+ + 2NO2 + 2 H2O

Nitration of benzene: HNO3 + H2SO4

H O N

OO H O S

O

O

O H+ H O N

OO

H+ HSO4

O N O + H2O

Nitronium ionsrong electrophile

ON

O NH

O

ON

H

O

ON

H

O

O

NH

O

ON

O

ONO2

Sulfonation of benzene: fuming sulfuric acid ( 发烟硫酸 ) 7% SO3 in H2SO4

SO

O

OS

O

O

OS

O

O OS

O O

O

SO

O

O+

SH O

O

OH

SO3H

SO3H+ H2O + H2SO4heat

The Friedel-Crafts alkylation of benzene: RX, AlCl3( or ether Lewis acid)

R······X······AlCl3δ+ δ-

E+:

R+ can rearrangement; Polyalkylations often occur.

C=C, H+

C-C-OH, acid

Other carbocation source

Limitations:

Problems:

Predict products for the reactions of benzene with the fol

lowing reagents.

Cl

Cl

+ HF

OH + BF3

(a)

(b)

(c)

(d)

+ AlCl3

+ AlCl3

The Friedel-Crafts Acylation of benzene:

RCOCl, AlCl3 (Lewis acid)

E+:

R O R

O O

Acylium ion 酰基正离子

RC

OC

R

O O AlCl3

RC

O

OC

R

O AlCl3

RC

Cl

O

AlCl3 RC

O

Cl AlCl3

RC

O

RC

O

The Gatterman-Koch formylation:——synthesis of genzaldehyde

AlCl3/CuClC H

O

+ CO + HCl

CO + HClH C Cl

O

The Clemmensen reduction: ——synthesis of alkylbenzenes.

RCOCl, AlCl3C R

O

aq HCl

Zn[Hg]CH2 R

The Clemmensen reduction

CH2CH2CH3

How to shnthesize n-propylbenzene from benzene?

CCH2CH3

O

S

o-

m-

p-(1) Reactivity: Electron donating group ( 给电子 ): Activiting ( 活化 ) Electron withdrawing ( 拉电子 ): deactivating ( 钝化 )(2) Orientation: o-, m-, p-, which is major?

The effects of substituents on the electrophilic aromatic substitution:

Reactivity and Orientation

CH3 CH3 CH3 CH3

+ +HNO3

H2SO4

NO2

NO2

NO2

H

H

H

H

H

Yield: 60% 4% 36%

Nitration of toluene

Why?

Toluene is about 25 times faster than benzene.

A) Activating groups: ortho-para directors活化，邻、对位定位基

-O-, -NR2, HO-, RO-, CH3CONH-, R-

( 和芳环碳相连的原子带部分负电荷 , 或有孤对电子 , 因 ) 此有给电子作用 .)

17-6

Alkyl groups, substituents with nonbonding electrons (O, N) can activate the aromatic ring.

OH

+ 3Br2H2O

OH

BrBr

Br

+ 3 HBr

B) Deactivating groups: Meta-Directors钝化，间位定位基

-+NR3, -NO2, -CF3, -CCl3, -CN, -SO3H, -CHO, RCO-, -COOH, -COOR, CH3CO-,

NO2

HNO3

H2SO4

NO2

NO2

NO2

NO2

+ +

6% 1% 93%

NO2

NO2

( 和芳环碳相连的原子带部分正电荷 , 因此有拉电子作用 .)

17-7

In general, deactivating substituents are groups with a positive charge (or a partial positive charge) on the atom bonded to the aromatic ring.

C) Halo substituents: Deactivating but ortho-para directors ( 卤代：钝化 , 但是邻对位定位基 )

Cl

HNO3

H2SO4

Cl

NO2

Cl

NO2

+

30% 70%

Cl

Cl

Cl

Cl

+

39% 55%

Cl2FeCl3

+

Cl

Cl

6%

Cl

17-8

Halo substitution: electron withdrawing groups, 吸电子基

Inductive effect explanation 诱导效应解释

S

E+

¦Ä+

¦Ä-

¦Ä-¦Ä+

S

E+¦Ä+

¦Ä-

¦Ä-

¦Ä+

Explanation of the orientaion

Resonance effect explanation共振效应解释

NH2 OH OCH3 Cl

Aniline Phenol Chlorobenzeneanisole

CH3

toluene

m- director

o-, p- director

CF3 NO O

Conclusion:-CF3 is a m-director 。

+ charges adjacent,unstable

o-

p-

m-

HE

CF3H

E

CF3H

E

CF3

HE

CF3

HE

CF3

HE

CF3

CF3

E

H

CF3

E

H

CF3

E

H

δ+

δ+

N

EH

N

EH

N

EH

O O OO O O

HE

N

HE

N

HE

NO O OO O O

H E

NH E

NH E

NO O O O O O

o-

p-

m-

Conclusion:-NO2 is a m-director 。

+ charges adjacent,unstable

Conclusion:-CH3 is a o- and p-director.

3°favorable

3°favorable

o-

p-

m-

HE

CH3H

E

CH3H

E

CH3

HE

CH3

HE

CH3

HE

CH3

CH3

E

H

CH3

E

H

CH3

E

H

o-

p-

m-

HE

OHH

E

OHH

E

OHH

E

OH

HE

OH

HE

OH

HE

OH

HE

OH

OH

E

H

OH

E

H

OH

E

H

Conclusion:-OH is a o- and p-director.

Especially stable

o-

p-

m-

HE

ClH

E

ClH

E

ClH

E

Cl

HE

Cl

HE

Cl

HE

Cl

HE

Cl

Cl

E

H

Cl

E

H

Cl

E

H

Conclusion:-Cl is a o- and p-director.

Especially stable

Notice: Friedel-Crafts reactions fail with strongly deactivated systems.

NH2

+ AlCl3

(-NHR, -NR2) NH2

+Cl3Al

OH

+ AlCl3

OH+

Cl3Al(OR)

Aniline and phenol (especialy aniline )does not undergo a Friedel-Crafts reaction

Orientation in disubstituted benzenes

两个取代基定位效应一致—共同指向位置

两个取代基定位效应不一致—由邻对位基确定指向位置 ; 如两个都是间位或邻对位定位基，由强者确定指向位置。

NHCOCH3

SO3H

CF3

NO2

OH

NO2

NHCOCH3

HO3S

CF3

NO2

OH NO2

biphenyl联苯

2) Nucleophilic aromatic substitution

Substrate: aryl halide ( 芳基卤 )Cl

NO2

OHNO2

+ OH- aq. NaHCO3

130CH+

ClNO2

NO2

OHNO2

NO2

+ OH- aq. NaHCO3

100CH+

ClNO2

NO2

O2NOH

NO2

NO2

O2N+ OH-

aq. NaHCO3

35C

H+

邻、对位有吸电子基有利。

Addition-elimination mechanismCl

NO2

+ OH- additionslow

OHCl

NO2

eliminationfast

OH-+ Cl-

O-

NO2

OH

NO2

+ Cl-

Cl

350¡æ(high pressure)

ONaNaOH HCl

OH

Br

K+NH2- NH2

-

NH3

NH2

NH2

(50%)

(50%)

14 14

14

14

Elimination-addition mechanism: benzyne 苯炔机理

base = NaNH2

or high pressure

3) Addition reactions of benzene derivatives

(1) Chlorination

ClCl

Cl

ClCl

Cl

Cl2hv

or high T, pFree radical mechanism

(2) Addition of hydrogen (reduction)

H2

catalystcatalyst: Pt, Pd, Ru, Rh, Ni

No

The Birch reduction 伯奇还原

Developed by the Australian chemist A.J. Birch

Benzene

NH3, EtOH

1,4-Cyclohexadiene

Na or K

Mechanism: similar as trans- reduction of alkyne with Na/NH3(liq.) (p-756)

1,2-Dimethylbenzene

NH3, EtOH

NaCH3 CH3

1,2-Dimethyl-1,4-cyclohexadiene 77-92 %

CH3 CH3

(o-xylene)

Methoxybenzene±½¼×ÃÑ

NH3, EtOH

LiOCH3 OCH3

1-Methoxy-1,4-cyclohexadiene 80 %

Sodium benzoate

NH3, EtOH

Na

(±½¼×ËáÄÆ)

COONa COONa

H3O+

COOH

89-52 %

electron donating给电子基，氢加在 2,5- 位

electron withdrawing拉电子基 , 氢加在 1,4- 位

4) Reactions of the side chain of alkylbenzenes

(1) Halogenation of the side chain benzylic radicals

useful in synthesis

Notice: 氯代产物复杂，除苄基位外还有 β 位取代产物。

hvCCl4

CH2Br

Benzyl bromide 64%

CH3

+ NBr

NBS

+ NH

Toluene

O

O

O

O

hv, CCl4

CHBr

CH2CH3NBS

CH3

(2) Oxidation of the side chain

The alkyl side chain with α - H on a benzene ring is oxi

dized to benzoic acid by chromic acid( 铬酸 ) or KMnO4.

CH2CH2CH3

1) KMnO4, OH-

2) H3O+

COOH

Benzoic acid 100% CH2CH2CH3

1) KMnO4, OH-

2) H3O+

C(CH3)3

COOH

C(CH3)3

+ O2

V2O5

450~500 °CO

O

O

5) phenols (17-15)

OH

OH

OH

OH

HO OH

1,2-Benzenediol(¶ù²è·Ó,ÁÚ±½¶þ·Ó)

1,3-Benzenediol(À×Ëö·Ó,¼ä±½¶þ·Ó£©

1,4-Benzenediol (¶Ô±½¶þ·Ó)

CH3

OH

CH3

OH

H3C OH

2-Methylphenol(ÁÚ-¼×·Ó£©

3-Methylphenol(¼ä-¼×·Ó£©

4-Methylphenol(¶Ô-¼×·Ó£©

Synthesis of phenol

in laboratory Ar-NH2

HONO Ar-N2+ H3O+

heat Ar-OH

Cl

350¡æ(high pressure)

ONaNaOH HCl

OH

industrial synthesis

Oxidization:

+ O295-135¡æ O O H Cumene hydroperoxide

(¹ý Ñõ» Ò̄ì±û»ù±½)

Hydrolytic rearrangement:

O O H H+, H2O

50-90¡æOH

O

+Acetone (±ûͪ £©

ArOHNaOH ArO-Na+ R-X

X = Cl, Br, I, OSO2R' or ,OSO2OR.

ArOR + NaX

Aspirin 阿斯匹林

Reactions of phenols

OH

COOHOCCH3

COOH

+ H+

O

+ CH3COOH

Salicylic acid (Ë®ÑîËᣩ

Acetic anhydride (ÒÒËáôû£©

Axetylsalicylic acid (ÒÒõ£Ë®ÑîËᣩ

(CH3CO)2O

A) Acidity

B) Acylation of hydroxyl group

White precipitate.

C) Electrophilic aromatic substitution

OH

+ 3Br2H2O

OH

BrBr

Br

+ 3 HBr

2,4,6-Tribromophenol (2,4,6-Èýäå±½·Ó£©

OH

+ Br2CCl4

OH

Br

+ HBr

OH

Br

+

OH

OH

OH

SO3H

SO3H

concdH2SO4

25¡æ

100¡æ

concd H2SO4, 100¡æ

equilibrium control

rate control

The o- and p- nitrophenol can be separated by steam distillation( 不蒸汽蒸馏 ).

OH OH OH

NO2

NO2

20% HNO3

25¡æ+

(30 - 40 %) (15 %)

D) Oxidation of phenols

OH O

O

K2Cr2O7-H2SO4

Notice: 在合成中酚羟基通常要保护，以防止氧化

p-Benzoquinone ( 对 - 苯醌 )

E) Reaction with FeCl3

phenol , 蓝紫色，烯醇的特殊性质。用来检验酚或烯醇结构。

6) Naphthalene 萘

αα

α α

β

β

β

β

1

2

3

45

6

7

89

10

NO2 SO3H

CH3

0.142 0.136

0.1400.139

1-nitronaphthaleneα-nitronaphthalene

5-methyl-2-naphthalenesulfonic acid5-methyl- β -naphthalenesulfonic acid

Reactions of naphthalene

Reactivity: naphthalene > benzene α- >β-

A) Substitution

+ Br2

CCl4

Br

H2SO4

SO3H

~60°C

> 150°C SO3H

84%

85%

equilibrium control

rate control

Notice: 一取代萘的定位效应也受环上原有取代基的控制。

+ CH3CCl

OAlCl3

CS2

CO CH3

+ CH3CCl

OAlCl3

PhNO2

C

O

CH3

CH3 CH3 NO2

B) Oxidation and reduction

O

O

CrO3, HOAc

O

O

CrO3, HOAcCH3 CH3

V2O5

400°CO

O

O

1,4-dihydronaphthalene1,4- 二氢萘

decalin十氢萘

C2H5OH

Na , NH3(l)

H H

H H

C2H5OH

Na , NH3(l)

H H

H H

OCH3OCH3

Pt, H2

high P, heating

Summary1. 理解苯分子的结构，并能用 RT ， VB ， MO 法解释其特

殊稳定性的原因。2. 会用 Hückel rule 判断环状共轭体系是否具有芳香性。3. 会命名苯的衍生物，苯作为母体或作为取代基。4. 熟悉苯的波谱特征。5. 熟练掌握苯及其衍生物的亲电芳香取代反应的历程、定

位规则，掌握卤代、硝化、磺化、 Fridel-Crafts 烷基化及酰基化反应，并能用于苯衍生物的合成。

6. 掌握苯的侧链反应特点：氧化、自由基卤代及其在有机合成中的应用。

7. 掌握苯酚的反应特点：羟基的反应、芳环上的反应。8. 了解苯的加成反应，尤其是催化加氢和 Berch reduction

反应的特点与机理。9. 了解卤代苯的亲核取代反应、萘的反应特点。

CH2CH2CH2CH3

O

Problems

How to synthesis the following compounds?

先酰化，再还原。

O

O

O

先酰化 - 还原 - 酰氯 - 酰化

NH2 NH2

NO2

and

NH2

NO2

NO2

Cl CH2CH2CH3

CH3CH2Br

Br

上官能团顺序：丙酰化－氯化－硝化

不能在酸性条件下直接硝化。应先把氨基酰化后再硝化。

磺酰化－溴化－自由基溴化苄基位

O

CH3

AlCl3+ C9H12O

Propose mechanism and predict the structure of the product.

Assignments

• T-1: 17-44, 46, 47, 49, 50, 51,

• 57,59, 61, 65

• T-2 （ selected ） : 5, 6, 7, 11, 12, 18, 19