2. Chapter 17 & 18 Aromatic chemistry Organic Chemistry, 6 th Edition L. G. Wade, Jr. Key Notes Aromaticity; Resonance Structure; Hückel rule; Electrophilic substitutions; Deactivating group; 有机化学 ORGANIC CHEMISTRY 主讲：王俊儒 87092829(O) 理学院应化系理科楼 2 层 C206 Homework ： 17-14; 17-16 （ b ） ; 17-22; (P580 ） 18-23; 18-25;(P624 ）

3. CONTENT  Structure & Physical Properties  Aromaticity & reactivity  Preparation of Ar compounds  Electrophilic substitutions  Effects of substituents on E.S. Synthesis of mono-, di- and tri-substituted benzenes  Other reactions Oxidation and reduction Nucleophilic Substitution

4. Sec 1 Structure & Physical Properties  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 C 6 H 6. Other related compounds with low C:H ratios had a pleasant smell, so they were classified as aromatic.

5. Kekul é Structure  Proposed in 1866 by Friedrich Kekul é, shortly after multiple bonds were suggested.  Failed to explain existence of only one isomer of 1,2-dichlorobenzene.

6. Resonance Structure  Each sp 2 hybridized C in the ring has an unhybridized p orbital perpendicular to the ring which overlaps around the ring.

7. Sec 1 Structure & Physical Properties  Each carbon contributes a p orbital  Six p orbitals overlap to give cyclic p system; 闭 合的共轭体系 ( 环状  电子流 )  Six p electrons delocalized throughout p system 高度离域 ( 无单双键之分 )  High electron density above and below plane of ring 平面结构，键角为 120 0 ， Planar

8. Sec 1 Structure & Physical Properties 芳香性 140 pm 146 pm 134 pm 微微米

9. Unusual Reactions  Alkene + KMnO 4  diol (addition) Benzene + KMnO 4  no reaction.  Alkene + Br 2 /CCl 4  dibromide (addition) Benzene + Br 2 /CCl 4  no reaction.  With FeCl 3 catalyst, Br 2 reacts with benzene to form bromobenzene + HBr (substitution!). Double bonds remain.

10. Sec 1 Structure & Physical Properties  Unusual Stability Hydrogenation of just one double bond in benzene is endothermic! Benzene is 150 kJ/mol (36 kcal/mol) more stable than might be expected for “ cyclohexatriene ”

11. Physical Properties Physical Properties of benzene 1. It is a colourless liquid with boiling point 80 o C. 2. It is insoluble in water but soluble in organic solvent. 3. It burns with a sooty flame and it is highly inflammable. 4. It is carcinogenic. 致癌物 ( 质 ) 的

12. Properties of Ar compounds  Many aromatic compounds have a characteristic aroma and burn with a smoky flame.  They are nonpolar, hydrophobic molecules which dissolve in organic solvents rather than water.  Aromatic molecules can interact by van der Waals interactions or with a cation through an induced dipole interaction.  Electrophilic substitution is the most common type of reaction. However, reduction is also possible.

13. Sec 2 Aromaticity and Reactivity  Reactivity 反应性 不易加成 ( 苯环骨架不断开 ) 发生取代 ( 亲电取代 E.S) 侧链反应  Aromaticity 芳香性化合物特点 大的不饱和度 (  ≧ 4)  =? ( 环状 ) 平面分子 易进行亲电取代反应 芳香性

14. Sec 2 Aromaticity and Reactivity  芳香性判别 (H ü ckel rules) 闭合的共轭体系 ( 环状  电子流 ) 4n+2

16. H ü ckel ’ s Rule  Once the aromatic criteria is met, Huckel ’ s rule applies.  If the number of pi electrons is (4N + 2) the compound is aromatic (where N is an integer)  If the number of pi electrons is (4N) the compound is antiaromatic.

17. Cyclopentadienyl Ions  The cation has an empty p orbital, 4 electrons, so antiaromatic.  The anion has a nonbonding pair of electrons in a p orbital, 6 e - ’ s, aromatic.

18. Which of the following is an aromatic compound? Non-aromatic Aromatic There is an sp 3 carbon in the ring, delocalization will not be complete. All carbons are sp 3 hybridized and it obeys Huckel’s rule.

19. Tropylium Ion

20. ◆ 薁◆ 薁 Zwitterionic 两性离子的

21. 薁

23. 并环戊二烯负离子

24. 空间障碍 环辛五烯

26. ◆ 大环芳香体系 具有交替的单双键的单环多烯烃，通称为轮烯（ annulenes ） 芳香性 共平面性或接近平面性，平面扭转又大于 0.1nm 轮内氢原子间没有或很少有空间排斥作用 π 电子数目符合 4n+2 规则 [18] 轮烯 ［ 10 ］轮烯 ［ 14 ］轮烯

28. 1mile=1.6 km 100m/s

30. Some New Allotropes  Fullerenes: 5- and 6-membered rings arranged to form a “ soccer ball ” structure.  Nanotubes: half of a C 60 sphere fused to a cylinder of fused aromatic rings.

31. Aromatic Heterocycles ---Pyridine  Heterocyclic aromatic compound.  Nonbonding pair of electrons in sp 2 orbital, so weak base, pK b = 8.8.

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

33. Aromatic Heterocycles

34. Basic or Nonbasic? Pyrimidine has two basic nitrogens. Imidazole has one basic nitrogen and one nonbasic. Purine?

35. Other Heterocyclics

36. Is the molecule below aromatic, anti- aromatic or non-aromatic? N N N H Aromatic

37. Larger Polynuclear Aromatic Hydrocarbons  Formed in combustion (tobacco smoke).  Many are carcinogenic.  Epoxides form, combine with DNA base. pyrene 芘

38. Fused Heterocyclic Compounds Common in nature, synthesized for drugs. tryptophan 色氨酸 benziodarone 苯碘达隆 ( 扩冠 ) Lysergic Acid Diethylamide （麦角酸二乙基酰胺 LSD ） quinine 奎宁 1820LSD

39. Summary  Aromaticity(?)  High Stability  Electrophilic Substitution RXs

40. Sec 3 Preparation of Ar compounds  Preparation Simple aromatic structures such as benzene, toluene, or naphthalene are isolated from natural sources and converted to more complex aromatic structures.

41. Reaction sites  Benzene ring  Side chain   -carbon

42. Sec 4 E.S Reaction of benzene  Electrophilic Substitution Reaction Nitration (Forming nitro-compound) Sulphonation (Forming sulphonic acid) Halogenation (Forming halobenzene) Friedal-Craft Alkylation (Forming alkylbenzene) Friedal-Craft Acylation (Forming carbonyl compound) 一代三化 : 卤代、硝化、磺化、富氏化

43. Sec 4 Electrophilic substitutions 一代三化反应 : 卤代、硝化、磺化、富氏化 An electrophilic substitution involves the substitution of one electrophile (a proton) from the aromatic ring with another electrophile. The aromatic ring remains intact.

44. Electrophilic Aromatic Substitution Electrophile substitutes for a hydrogen on the benzene ring.  Although benzene ’ s pi electrons are in a stable aromatic system, they are available to attack a strong electrophile to give a carbocation.  This resonance-stabilized carbocation is called a sigma complex because the electrophile is joined to the benzene ring by a new sigma bond.  Aromaticity is regained by loss of a proton.

45. 1. E. S Mechanism Step 1: Attack on the electrophile forms the sigma complex. Step 2: Loss of a proton gives the substitution product. Addition to benzene is endothermic, not normally seen. Formation of sigma complex is rate-limiting

46. σ 络合物 一元取代苯 ++  亲电试剂 π 络合物 σ 络合物 Resonance hybrid

47. 亲电取代和亲电加成反应能量变化示意图

48. Bromination of Benzene

49.   Electrophiles used in E.S    Cl-Cl + - - AlCl 3, Br-Br + - - FeBr 3, I +  + NO 2, SO 3,  R +, or R-Cl + - - AlCl 3, RC + =O

50.   Electrophiles used in E.S    亲电试剂的产生

51. 2. Aromatic Halogenation Electrophilic aromatic substitution reaction begins in a similar way to electrophilic alkene addition reaction  FeBr 3 catalyst is needed for bromination of benzene to occur FeBr 3 polarizes Br 2 molecule making it more electrophilic Polarization makes FeBr 4 - Br + species that reacts as if it were Br +

52. Bromination of Benzene  Requires a stronger electrophile than Br 2.  Use a strong Lewis acid catalyst, FeBr 3.

53. Energy Diagram for Bromination

55. Chlorination and Iodination  Chlorination is similar to bromination. Use AlCl 3 as the Lewis acid catalyst.  Iodination requires an acidic oxidizing agent, like nitric acid, which oxidizes the iodine to an iodonium ion.

56. Fluorine is too reactive to give mono-fluorinated products Iodine itself is unreactive toward aromatic rings

58. 3. Aromatic Nitration  Aromatic rings can be nitrated with a mixture of concentrated nitric and sulfuric acids The electrophile is the nitronium ion, NO2+ which is generated from HNO3 by protonation and loss of water The nitronium ion reacts with benzene to yield a carbocation intermediate, and loss of H + The product is a neutral substitution product, nitrobenzene

59. Nitration of Benzene Use sulfuric acid with nitric acid to form the nitronium ion electrophile. NO 2 + then forms a sigma complex with benzene, loses H + to form nitrobenzene.

60. Nitration of Toluene  Toluene reacts 25 times faster than benzene. The methyl group is an activating group.  The product mix contains mostly ortho and para substituted molecules.

61. Sigma Complex Intermediate is more stable if nitration occurs at the ortho or para position.

62. Energy Diagram

63. 4. Aromatic Sulfonation  Sulfonation -reversible reaction  Sulfur trioxide, SO 3, in fuming sulfuric acid is the electrophile.

65. Desulfonation  All steps are reversible, so sulfonic acid group can be removed by heating in dilute sulfuric acid.  This process is used to place deuterium in place of hydrogen on benzene ring. Benzene-d 6

66. 5. Friedel-Crafts Alkylation Rearrangement  Rearrangement may occur in alkylation

67. Friedel-Crafts Alkylation

69.  富氏烷基化反应的局限性

71. Alkylation of Aromatic Rings  A skeletal rearrangement of the alkyl carbocation electrophile sometimes occurs during a Friedel-Crafts reaction, particularly when a primary alkyl halide is used  Carbocation rearrangements occur either by hydride shift or alkyl shift Alkylation of benzene with 1-chloro-2,2- dimethylpropane yields (1,1- dimethylpropyl)benzene

72. 6. Friedel-Crafts Acylation  Friedel-Crafts Acylation

73. Friedal – Craft Acylation

74. Freidel-Crafts Acylation

76. ? Predict the products of the following reactions

78. 克莱门森 Clemmenson 还原法：盐酸中用锌／ 汞齐来还原羰基为亚甲 基的反应 Solutions 思考：如何从苯合成正丁基苯？

79. Predicting the Product of a Carbocation Rearrangement  The Friedel-Crafts reaction of benzene with 2-chloro-3-methylbutane in the presence of AlCl 3 occurs with a carbocation rearrangement. What is the structure of the product?

80. Predicting the Product of a Carbocation Rearrangement  Strategy  A Friedel-Crafts reaction involves initial formation of a carbocation, which can rearrange by either a hydride shift or an alkyl shift to give a more stable carbocation Draw the initial carbocation, assess its stability, and see if the shift of a hydride ion or an alkyl group from a neighboring carbon will result in an increased stability  The initial carbocation is a secondary one that can rearrange to a more stable tertiary one by a hydride shift  Use the more stable tertiary carbocation to complete the Friedel-Crafts reaction

81. Solution

82. Review ： 苯环亲电取代反应的特征  多数在酸性溶液中, 以亲电试剂取代苯环中质子方式进行  反应机理 : 先加成后消除  亲电试剂 :Cl +,Br +,I + + NO 2, SO 3, R +, RC + =O   - 络合物是其活性中间体  定位效应可用极性交替理论和饱和碳链电荷逐步消长效应来解释 - - + + + ++ + + - - - - -

83. Sec 5 Effects of substituents on E.S of substituted benzenes  反应活性  定位

84. Substituent Effects in Electrophilic Substitutions Substituent effects in the electrophilic substitution of an aromatic ring  Substituents affect the reactivity of the aromatic ring Some substituents activate the ring, making it more reactive than benzene Some substituents deactivate the ring, making it less reactive than benzene Relative rates of aromatic nitration

85. Substituent Effects in Electrophilic Substitutions The three possible disubstituted products – ortho, meta, and para – are usually not formed in equal amounts The nature of the substituent on the ring determines the position of the second substitution  Substituents affect the orientation of the reaction

86. Substituent Effects in Electrophilic Substitutions Electrostatic potential maps of benzene, phenol (activated), chlorobenzene (weakly deactivated), and benzaldehyde (more strongly deactivated) The – OH substituent makes the ring more negative (red) The – Cl makes the ring less negative (orange) The – CHO makes the ring still less negative (yellow)

87. 1,2- 二氯苯 1,4 二氯苯 邻氯甲苯 对氯甲苯

88. 极少量 硝基苯硝化极为困难 TNT

89. 苯磺酸与发烟硫酸反应，提高反应温度磺化 间二苯磺酸 邻甲苯磺酸 对甲苯磺酸

90. -- ++ -- ++ -- ++ 极性交替 + + - - + --

92. Summary of Activators

93. greatest effect on the carbon atoms ortho and para

94. Activators and Deactivators  If the substituent on the ring is electron donating, the ortho and para positions will be activated.  If the group is electron withdrawing, the ortho and para positions will be deactivated.

95. 邻、对定位 Ortho- & para - directing 间位 Meta- directing 制钝 Strongly Deactivating 致活 Strongly Activating 1类1类 2类2类

96.   定位基的特点   Activating groupsDeactivating groups Powerful-NH 2,-NHR,-NR 2, -OH,-O - -NO 2, - N + R 3 (+R)(-R,-I) (-I) Intermediate-OR,-NHCOR,-CN,-CHO,-COR, -SO 3 H,-CO 3 H (+R,-I)(-R,-I) Weak-ph(+R); -R(+R,+I) Ortho,para -F,-Cl,-Br,-I(+R,-I)

97. Summary

99.   定位基的特点    1 类 ( 邻对位定位基 ) 直连原子有孤对电子,p-  共轭 苯环电子云密度 致活，反应活性  2 类（间位定位基） 吸电子基 极性不饱和键 C=O 等 苯环电子云密度 致钝，反应活性 X is a deactivating group towards E.S.

100.  -OH group is an highly activating group, by exerting +M effect (at the ortho and para positions) : E.S. Reactions of phenol

101.  Nitration Mononitration by dilute HNO 3  Sulphonation Dilute H 2 SO 4  Halogenation Trisubstitution without halogen carrier E.S. Reactions of phenol

102.  Halogenation of phenol E.S. Reactions of phenol Observation : decolorization of bromine formation of white ppt.

103. (X is a deactivating group towards E.S.), but  The reaction is in general slower than benzene (X is a deactivating group towards E.S.), but faster at ortho and para position (o,p directing). E.S. Reactions of Halobenzene major minor

104.   多取代基定位规律    1 类定位基决定反应位置与反应活性  同类定位基, 强者定 混合物

105.   影响定位规律的因素   ▲ 空间效应 ▲ 温度效应 0 ℃ 100 ℃

106. 取代基对芳环亲电取代反应的影响 Sec 5 取代基对芳环亲电取代反应的影响 Questions

107. Sec 6 Synthesis of mono-, di- and tri-substituted benzenes Synthetic planning I  When planning the synthesis of an aromatic compound, it is best to work backwards from the product in simple stages (retrosynthesis 反 向合成 ).  If the sub-stituent present cannot be added directly to the aromatic ring, it is best to consider what functional group could be transformed to give the desired substituent.

108. Sec 6 Synthesis of mono-, di- and tri-substituted benzenes Many functional groups can be obtained by converting functional groups already added.  An amino group can be obtained by reduction of a nitro group then converted to a large range of other functional groups.  Alkyl groups can be oxidized to a carboxylic acid group which can in turn be converted to other functional groups.

109. Or Fe/HCl

115. Removable substituents

116. Br

117. Removable substituents

118. Sec 7 other reactions 1. 芳烃侧链的反应  A 、光照或加热条件下  – 卤代反应 Benzylic halides are 100 times more reactive than primary halides via S N 2

119. At side chain Substitution at side chain

120. B 、芳环侧链的氧化反应（  -C ） Oxidation of alkyl benzene With MnO 4 - /H + No oxidation for C 、芳胺经过重氮盐的反应

122. (1) 加氢反应 环己烷 2 、加成反应

123. 二取代和多取代苯氢化后通常得到立体异构体的混合物，其中主 要是热力学上有利的产物。 顺 -1,2- 二甲基环己烷 伯奇（ Birch ）还原 1,4- 环己二烯

125. (2) 加氯 紫外线照射或过氧化物存在，苯与氯气可发生自由基加成 1,2,3,4,5,6- 六氯环己烷 ( 六六六 )

126. β- 异构体 γ- 异构体 ( 产物较多 ) ( 杀虫效果最强 ) 反应历程

127. 3 、 Nucleophilic Substitution 芳环亲核取代反应？  通常苯是不会发生亲核反应 当亲核负离子接近时， pi- 电子云会对它 产生排斥；氢负离子碱性非常强，难离去。  S N Ar Reaction （芳环亲核取代反应）  当苯环上具有一个或多个强的吸电子基团，并且具 有一个较好的离去基团（如卤素）时，亲核取代反应 可以在不太激烈的条件下发生 Activated Positions

128. 3 、 Nucleophilic Substitution

129. Practice: Synthesizing Polysubstituted Benzenes 3. 从苯合成正丁基苯

130.  如何实现下列合成？ Examples:

131.  如何实现下列合成？

132. Sec 7 其它芳烃的化学性质 1. 萘 萘比苯更容易发生氧化、加成和取代反应，一般 а 位比 β 位活泼 邻苯二甲酸酐 a 氧化反应

133. b 加成反应： 顺十氢化萘 反十氢化萘 1,4- 二氢化萘 1,2,3,4- 四氢化萘

135. c 亲电取代反应： 浓 °C α 位硝化比苯快 750 倍，即使 β 位也比苯硝化快 50 倍

136. °C

138. Summary  芳香性化合物结构特征与芳香性判别 Aromaticity  亲电取代 Electrophilic substitution  定位效应 Substituent effects

139. The END