1. Chapter 9 Aromatic compounds 芳香化合物
Text 1: chapter 16, 17
Text 2: 第七章

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

3. 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).

4. The Kekule Structure for benzene 苯的克库勒结构
1. The Structure of benzene (16-2, 3)
The Kekule Structure for benzene 苯的克库勒结构
　Proposed in 1866 by Friedrich Kekulé, shortly after multiple bonds were suggested.
　Failed to explain existence of only one isomer of 1,2-dichlorobenzene.
Same compund

5. Modern theories of the structure of benzeneRT VB MO

6. The unusual stability of benzene
Hydrogenation of just one double bond in benzene is endothermic（吸热）!

7. Differences in Reactions between alkene and benzene

8. Aromatic Requirements
2. Aromaticity芳香性
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

9. 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.

10. Hückel’s Rule （休克尔规则）
The (4n+2) pi-Electron Rule
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.

11. Other aromatic compounds
(1) polynuclear aromatic hydrocarbons
(PAH, 多核芳烃,16-10)
Fused aromatic compounds稠环芳烃

12. 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)

13. (2) [N]annulenes (轮烯)
[4]Annulene is antiaromatic (4N e-’s)
[8]Annulene would be antiaromatic, but it’s not planar, so it’s nonaromatic.
[10]Annulene is aromatic except for the isomers that are not planar.
Larger 4N annulenes are not antiaromatic because they are flexible enough to become nonplanar.

14. Nonaromatic
非芳香性
[8]annulene
[10]annulene
nonaromatic
[14]annulene
nonaromatic
[16]annulene
Antiaromatic
if planar
[18]annulene
Aromatic if planar

15. Azulene 奥
The dipole moment is 1.0D
( aromatic 具有芳香性)
(aromatic)
Problem: Which molecule is more stable?
Answer: (A)

16. MO Derivation of Hückel’s Rule
=>
Lowest energy MO has 2 electrons.
Each filled shell has 4 electrons.

17. The Polygon Rule多边形规则
ring
Number of
πelectrons π* n E

18. Cyclopentadienyl Ions 环戊二烯离子
Aromatic ions
Cyclopentadienyl Ions 环戊二烯离子
4 electrons, antiaromatic.
6 electrons, aromatic.
Acidity

19. Tropylium Ion 卓翁离子 Aromatic ions Cycloheptatrienyl cation 环庚三烯阳离子
6 p electrons and an empty p orbital.
Aromatic: more stable than open chain ion

20. Dianion of [8]Annulene [8]轮烯二价阴离子
Aromatic ions
Dianion of [8]Annulene [8]轮烯二价阴离子
Cyclooctatetraenyl dianion
环辛四烯二价阴离子
10 p electrons, aromatic.

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

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

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

24. Basic or Nonbasic? Pyrimidine（嘧啶） has two basic nitrogens.
Imidazole（咪唑） has one basic
nitrogen and one nonbasic.
Purine（嘌呤） ?

25. =>

26. 3. Nomenclature of benzene derivatives
Monosubstituted benzenes
“XXbenzene” ， XX苯
Fluorobenzene
(氟苯）
Chlorobenzene
（氯苯）
Bromobenzene
（溴苯）
Nitrobenzene
(硝基苯）

27. Methylbenzene
Toluene
(甲苯）
Ethylbenzene
（乙苯）
Hydroxybenzene
Phenol
（苯酚）
Aminobenzene
Aniline
（氨基苯， 苯胺）
Benzenesulfonic acid
苯磺酸
Benzoic acid
苯甲酸
Acetophenone
苯乙酮
Anisole
苯甲醚

28. (2) disubstituted benzenes 1,2-; 1,3-; 1,4- o- (邻), m- (间), p- (对)
1,2-Dibromobenzene
o-Dibromobenzene
邻二溴苯
1,3-Dibromobenzene
m-Dibromobenzene
间二溴苯
1,4-Dibromobenzene
p-Dibromobenzene
对二溴苯

29. 1,2-Dimethylbenzene 1,3-Dimethylbenzne 1,4-Dimethylbenzene
o-xylene 　 m-xylene p-xylene
2-Nitrobenzoic acid Nitrobenzic acid Nitrobenzic acid
o-Nitrobenzoic acid m-Nitrobenzoic acid p-Nitrobenzoic acid

30. (3) benzene as substituent: phenyl group (苯基)， Ph-
Butylbenzene
2-Phenyl-2-butene
2-Phenylheptane
Benzyl group (苄基),Bn-
Aryl group (芳基),Ar-
Arene = Aromatic hydrocarbon

31. and spectroscopy of aromatic compounds
4. Physical properties
and spectroscopy of aromatic compounds
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.

32. spectroscopy of aromatic compounds
UV: 254 nm (B 带)
IR: 3030 (C-H), 1600 (skeleton), 1500 cm-1
1H NMR: 7~9ppm
MS:

34. 1-phenylpropan-2-one

35. Chapter 9 Aromatic compounds
Assignments:
T-1: 16-27, 28, 30, 33, 36

36. 5. Reactions of benzene and its derivatives
Chapter 9 Aromatic compounds
5. Reactions of benzene and its derivatives
(Chapter 17)

37. 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

38. 1) Electrophilic aromatic substitution reactions
17-2
17-3
17-4
17-10
17-11

39. Electrophilic addition-elimination mechanism
亲电加成-消除机理
Step 1: addition
Arenium ion (芳基正离子) intermediate
σ- complex (σ-络合物）
Step 2: elimination

40. reaction coordination
TS 1
rate-limiting step
TS 2
Eact2
Eact1
σ-complex
reactants
product
reaction coordination
The reaction-energy diagram (反应能线图)

41. Halogenation of benzene: X2, FeX3
Reactivity: F2 > Cl2 > Br2 > I2

42. Nitration of benzene: HNO3 + H2SO4
Nitronium ion
srong electrophile

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

44. Limitations: The Friedel-Crafts alkylation of benzene:
RX, AlCl3( or ether Lewis acid)
R······X······AlCl3 δ+ δ-
E+:
Other carbocation source
C=C, H+
C-C-OH, acid
Limitations:
R+ can rearrangement;
Polyalkylations often occur.

45. Problems:
Predict products for the reactions of benzene with the following reagents.

46. The Friedel-Crafts Acylation of benzene: RCOCl, AlCl3 (Lewis acid)
Acylium ion
酰基正离子

47. The Gatterman-Koch formylation: ——synthesis of genzaldehyde

48. The Clemmensen reduction: ——synthesis of alkylbenzenes.
How to shnthesize n-propylbenzene from benzene?

49. Reactivity and Orientation
The effects of substituents on the electrophilic aromatic substitution:
Reactivity and Orientation o- m- p-
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?

50. Nitration of toluene
Yield: 60% % %
Toluene is about 25 times faster than benzene.
Why?

51. A) Activating groups: ortho-para directors 活化，邻、对位定位基
17-6
-O-, -NR2, HO-, RO-, CH3CONH-, R-
Alkyl groups,
substituents with nonbonding electrons (O, N)
can activate the aromatic ring.
(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.)

52. B) Deactivating groups: Meta-Directors 钝化，间位定位基
17-7
-+NR3, -NO2, -CF3, -CCl3, -CN, -SO3H, -CHO, RCO-,
-COOH, -COOR, CH3CO-,
In general, deactivating substituents are groups with a positive charge (or a partial positive charge) on the atom bonded to the aromatic ring.
(和芳环碳相连的原子带部分正电荷, 因此有拉电子作用.)

53. C) Halo substituents: Deactivating but ortho-para directors (卤代：钝化, 但是邻对位定位基)
17-8
Halo substitution: electron withdrawing groups, 吸电子基

54. Inductive effect explanation 诱导效应解释
Explanation of the orientaion
Inductive effect explanation 诱导效应解释

55. Resonance effect explanation 共振效应解释
m- director
o-, p- director

56. o- + charges adjacent, unstable p- Conclusion: -CF3 is a m-director。δ+ o-
+ charges adjacent,
unstable δ+ p-
Conclusion:
-CF3 is a m-director。 m-

57. o-
+ charges adjacent,
unstable p-
Conclusion:
-NO2 is a m-director。 m-

58. o-
3°favorable
Conclusion:
-CH3 is a o- and p-director. p-
3°favorable m-

59. o-
Especially stable p-
Conclusion:
-OH is a o- and p-director. m-

60. o-
Especially stable p-
Conclusion:
-Cl is a o- and p-director. m-

61. Notice: Friedel-Crafts reactions fail with strongly deactivated systems.
Aniline and phenol (especialy aniline )does not undergo a Friedel-Crafts reaction

62. 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。
biphenyl 联苯

63. 2) Nucleophilic aromatic substitution
Substrate: aryl halide (芳基卤)
邻、对位有吸电子基有利。

64. Addition-elimination mechanism
Elimination-addition mechanism: benzyne 苯炔机理
base = NaNH2 or
high pressure

65. 3) Addition reactions of benzene derivatives
(1) Chlorination
Free radical mechanism
(2) Addition of hydrogen (reduction) No

66. The Birch reduction 伯奇还原
Developed by the Australian chemist A.J. Birch
Mechanism: similar as trans- reduction of alkyne with Na/NH3(liq.)
(p-756)

67. electron donating
给电子基，氢加在2,5-位
electron withdrawing
拉电子基, 氢加在1,4- 位

68. 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。

69. (2) Oxidation of the side chain
The alkyl side chain with α - H on a benzene ring is oxidized to benzoic acid by chromic acid(铬酸) or KMnO4.

70. 5) phenols (17-15)

71. Synthesis of phenol
in laboratory
industrial synthesis

72. Reactions of phenols Aspirin 阿斯匹林 A) Acidity
B) Acylation of hydroxyl group
Aspirin 阿斯匹林

73. C) Electrophilic aromatic substitution
White precipitate.

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

75. D) Oxidation of phenols
p-Benzoquinone
(对-苯醌)
Notice: 在合成中酚羟基通常要保护，以防止氧化
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。

76. 6) Naphthalene 萘
0.142
0.136
0.140
0.139 α β 1 2 3 4 5 6 7 8 9 10
1-nitronaphthalene
α-nitronaphthalene
5-methyl-2-naphthalenesulfonic acid
5-methyl- β -naphthalenesulfonic acid

77. Reactions of naphthalene
Reactivity: naphthalene > benzene
α- >β-
A) Substitution
rate control
equilibrium control

78. Notice: 一取代萘的定位效应也受环上原有取代基的控制。

79. B) Oxidation and reduction

80. 1,4-dihydronaphthalene
1,4-二氢萘
decalin十氢萘

81. Summary 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。
会用Hückel rule 判断环状共轭体系是否具有芳香性。
会命名苯的衍生物，苯作为母体或作为取代基。
熟悉苯的波谱特征。
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。
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。
掌握苯酚的反应特点：羟基的反应、芳环上的反应。
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。
了解卤代苯的亲核取代反应、萘的反应特点。

82. Problems How to synthesis the following compounds? 先酰化，再还原。
先酰化-还原-酰氯-酰化

83. 不能在酸性条件下直接硝化。应先把氨基酰化后再硝化。
上官能团顺序：
丙酰化－氯化－硝化
磺酰化－溴化－自由基溴化苄基位

84. Propose mechanism and predict the structure of the product.

85. Assignments
T-1: , 46, 47, 49, 50, 51,
57,59, 61, 65
T-2 （selected）: 5, 6, 7, 11, 12, 18, 19