Chap 15 Electrophilic aromatic substitution ( 芳香族亲电取代）

1. Chap 15 Electrophilic aromatic substitution (芳香族亲电取代） 15.1 Electrophilic aromatic substitution reactions These reactions are of the general type shown below; E+-------Electrophilic reagent 亲电试剂

2. Fig 15.1 Electrophilic aromatic substitution reactions.

3. 15.2 A general mechanism for electrophilic aromatic substitution（芳香族亲电取代反应机理）: Arenium ions（芳基离子） π A considerable body of experimental evidence indicates that electrophiles attack the πsystem of benzene to form a delocalized nonaromatic carbocation known as an arenium ion (or sometimes as a σcomplex)

5. We wish to show the mechanism using the modern formula for benzene.

6. Fig 15.2 The potential energy diagram for an electrophilic aromatic substitution reaction.

7. 15.3Halogenation of benzeneBenzene does not react with bromine or chlorine unless a Lewis acid is present in the mixture. When Lewis acids are present, however, benzene reacts readily with bromine or, chlorine, and the reactions give bromobenzene and chlorobenzenein good yields.

8. Fluorine (F2) reacts so rapidly with benzene that aromatic fluorination requires special conditions and special types of apparatus. Iodine (I2), on the other hand, is so unreactive that a special technique has to be used to effect direct iodination; the reaction has to be carried out in the presence of an oxidizing agent such as nitric acid:

9. The mechanism for aromatic bromination is as follows;

10. 15.4 Nitration of benzene Benzene reacts slowly with hot concentrated nitric acid to yield nitrobenzene. The reaction is much faster if it is carried out by heating benzene with a mixture of concentrated nitric acid and concentrated sulfuric acid

11. Concentrated sulfuric acid increases the rate of the reaction by increasing the concentration of the electrophile-the nitronium ion(NO2+)

12. The nitronium ion reacts with benzene by attacking the πcloud and forming an arenium ion

13. 15.5 Sulfonation of benzene 苯的磺化 Benzene reacts with fuming sulfuric acid at room temperature to produce benzene sulfonic acid. Fuming sulfuric acid is sulfuric acid that contains added sulfur trioxide (SO3)

14. The mechanism of sulfonation

15. We may remove the sulfonic acid group by desulfonation We shall see later that sulfonation and desulfonation reactions are often used in synthetic work.

16. 15.6Friedel-Crafts alkylation付瑞德尔-克拉夫茨烷基化 A general equation for a Friedel-Crafts alkylation reaction is the following:

17. The mechanism for this reaction

18. More Friedel-Crafts alkylation

19. 15.7 Friedel-Crafts Acylation付瑞德尔-克拉夫茨酰基化

20. Friedel-Crafts acylations can also be carried out using carboxylic acid anhydrides（酸酐）.

21. The mechanism for Acylation of Friedel-Crafts

22. 15.8Limitations（限制）of Friedel-Crafts reactions 1. Form the more stable carbocation.

23. 2. Friedel-Crafts reactions do not occur when powerful electron-withdrawing groups are present on the aromatic ring or when the ring bears an –NH2, -NHR, or –NR2 group

24. The amino groups, -NH2, -NHR, and –NR2, are changed into powerful electron-withdrawing groups by the Lewis acids used to catalyze Friedel-Crafts reactions

25. 3 Aryl and vinylic halides can not be used as the halide component because they do not form carbocations readily.

26. Polyalkylations often occur (经常发生多烷基化） Alkyl groups are electron-releasing groups, and once one is introduced into the benzene ring it activates the ring toward further substitution.

27. 15.9 Synthetic applications of Friedel-Crafts acylations: The Clemmensen reduction(克莱门森还原）

29. Target molecule

30. 15.10 Effect of substitutions on reactivity and orientation取代基在反应性和定向方面的效应

31. We can divide substituent groups into two classes according to their influence on the reactivity of the ring. Those that cause the ring to be more reactive than benzene itself we call activating groups(活化基). Those that cause the ring to be less reactive than benzene we call deactivating groups(钝化基).

32. 15.10A Activating groups: Ortho-para directors The methyl group is an activating group and an ortho-para director. Toluene reacts considerably faster than benzene in all electrophilic substitutions.

33. When we nitrate toluene with nitric and sulfuric acids, we get mononitrotoluenes in the following relative proportions. Therefore, methyl group is ortho-para director group.

34. All alkyl groups are activating groups, and they are all also ortho-para directors. The methoxy group, CH3O- and acetamido group, CH3CONH-, are strong activating groups and both are ortho-para directors.

35. The hydroxyl group and the amino group are very powerful activating groups and are also powerful ortho-para directors.

36. 15.10B Deactivating groups: Meta-Directors

37. The nitro group(-NO2), the carboxyl group (-COOH), the sulfo group (-SO3H), and the trifluoromethyl group (-CF3), are also meta directors.

38. 15.10C Halo substituents: Deactivating ortho-para directors The chloro and bromo groups are weak deactivating groups. But they are ortho-para directors.

39. Electrophilic substitutions of Chlorobenzene Therfore, chloro and bromo are ortho-para directors.

40. 15.10DClassification of substituents

41. 15.11 Theory of substituent effects on electrophilic aromatic substitution 15.11A Reactivity: The effect of electron-releasing and electron-withdrawing groups (拉电子和推电子的效应） We find that the relative rates of the reactions depend on whether S（取代基）withdraws or release electrons. If S is an electron-releasing group, the reaction occurs faster than the corresponding reaction of benzene. If S is an electron-withdrawing group, the reaction is slower than that of benzene

43. 15.11B Inductive and resonance effects: Theory of orientation诱导效应和共振效应---定位理论

44. Inductive effect explanation诱导效应解释 Ortho-Para directors 邻对位定位基 由于苯环连有推电子基，使苯环产生极性交替，结果苯环的邻对位电子云密度较间位高，所以亲电试剂（E+)进攻邻对位。

45. 15.11C Meta-Directing groups 间位定位基 由于苯环连有拉电子基，使苯环产生极性交替，结果苯环的间位电子云密度较邻对位高，所以亲电试剂（E+)进攻间位。

46. Resonance effect explanation共振效应解释

48. The trifluoromethyl group is a powerful meta director.

49. 15.11D Ortho-Para-Directing groups (邻对位定位基） Do you know why E+ attacks ortho and para position ?