2. © 2011 Pearson Education, Inc. 1 Chapter 15 Aromaticity Reactions of Benzene Organic Chemistry 6 th Edition Paula Yurkanis Bruice

3. © 2011 Pearson Education, Inc. 2 Aromatic Compounds Are Unusually Stable Benzene is an aromatic compound

4. © 2011 Pearson Education, Inc. 3 Benzene is unusually stable because of electron delocalization Compounds with unusually large resonance energies, such as benzene, are called aromatic compounds

5. © 2011 Pearson Education, Inc. 4 Criteria for Aromaticity 1. A compound must have an uninterrupted cyclic cloud of  electrons above and below the plane of the molecule: 2. The  cloud must contain an odd number of pairs of  electrons, or 4n + 2 (n = 0, 1, 2 …) total electrons.

6. © 2011 Pearson Education, Inc. 5 Hückel’s Rule For a planar, cyclic compound to be aromatic, its uninterrupted  cloud must contain (4n + 2)  electrons, where n is any whole number Why? Pattern of bonding orbitals of planar cyclic  systems (e.g., benzene): Needs 4n + 2 (n = 0, 1, 2, 3…) electrons to fill orbitals

7. © 2011 Pearson Education, Inc. 6 Monocyclic hydrocarbons with alternating single and double bonds are called annulenes: Cyclobutadiene and cyclooctatetraene are not aromatic, because they have an even number of  electron pairs Cyclooctatetraene is a stable compound because it is large enough to form a tub shape, thereby removing degenerate orbitals

8. © 2011 Pearson Education, Inc. 7 Cyclopentadiene does not have an uninterrupted ring of p orbital-bearing atoms not aromatic not aromatic Cyclopentadienyl cation has an even number of  electron pairs Cyclopentadienyl anion has an uninterrupted ring of  orbital-bearing atoms and an odd number of  electron pairs

9. © 2011 Pearson Education, Inc. 8 The resonance hybrid shows that all the carbons in the cyclopentadienyl anion are equivalent Each carbon has exactly one-fifth of the negative charge associated with the anion

10. © 2011 Pearson Education, Inc. 9 These compounds consist of fused benzene rings and are aromatic: Any compound consisting of fused benzene rings is aromatic

11. © 2011 Pearson Education, Inc. 10 Aromatic Heterocyclic Compounds A heterocyclic compound has ring atoms other than carbon The heteroatom donates either one or two electrons to the  system Heteroatom donates two electronsHeteroatom donates one electron

12. © 2011 Pearson Education, Inc. 11 Pyridine Is Aromatic

13. © 2011 Pearson Education, Inc. 12 Pyrrole Is Aromatic The lone-pair electrons on the nitrogen atom of pyrrole are  electrons

14. © 2011 Pearson Education, Inc. 13 Furan and thiophene are aromatic compounds like pyrrole

15. © 2011 Pearson Education, Inc. 14 Examples of Heterocyclic Aromatic Compounds

16. © 2011 Pearson Education, Inc. 15 DNA & RNA Bases Are Aromatic Purine basesPyrimidine bases These heterocycles are aromatic because of amide resonance:

17. © 2011 Pearson Education, Inc. 16 The Effect of Aromaticity on the pK a Values of Some Compounds

18. © 2011 Pearson Education, Inc. 17 Why is the pK a of cyclopentadiene so much lower than that of ethane? The conjugate base is aromatic:

19. © 2011 Pearson Education, Inc. 18 Aromaticity influences chemical reactivity: The cycloheptatrienyl cation is aromatic:

20. © 2011 Pearson Education, Inc. 19 A compound is antiaromatic if it is a planar, cyclic, continuous loop of p orbitals with an even number of pairs of  electrons: Antiaromaticity Antiaromatic compounds are highly unstable, but the nonplanar versions are stable

21. © 2011 Pearson Education, Inc. 20 Antiaromaticity is important in medicine and biochemistry Stabilization of either the flat (aromatic) or the butterfly form influences a flavoenzyme’s redox potential: The tricyclic antipsychotics interact with the dopamine receptor because of the butterfly shape: 8-electron ring

22. © 2011 Pearson Education, Inc. 21 A Molecular Orbital Description of Aromaticity and Antiaromaticity Aromatic compounds are stable because they have filled bonding  molecular orbitals:

23. © 2011 Pearson Education, Inc. 22 Nomenclature of Monosubstituted Benzenes Some are named by attaching “benzene” after the name of the substituent:

24. © 2011 Pearson Education, Inc. 23 Some have to be memorized:

25. © 2011 Pearson Education, Inc. 24 A benzene substituent is called phenyl. A benzene substitutuent with a methylene group is called benzyl.

26. © 2011 Pearson Education, Inc. 25 Benzene is either the base name or the substituent (phenyl): Aryl group (Ar) is the general term for either an unsubstituted or a substituted phenyl group

27. © 2011 Pearson Education, Inc. 26 Aromatic compounds such as benzene undergo electrophilic aromatic substitution reactions:

28. © 2011 Pearson Education, Inc. 27 Benzene is a nucleophile that reacts with an electrophile An electrophilic substitution yields an aromatic product, which is significantly more stable than the addition reaction

29. © 2011 Pearson Education, Inc. 28 Reaction Coordinate Diagrams for the Two Benzene Reactions

30. © 2011 Pearson Education, Inc. 29 There are five common electrophilic aromatic substitution reactions: 1. Halogenation 2. Nitration 3. Sulfonation 4.Friedel–Crafts acylation 5.Friedel–Crafts alkylation

31. © 2011 Pearson Education, Inc. 30 General Mechanism for Electrophilic Aromatic Substitution of Benzene

32. © 2011 Pearson Education, Inc. 31 Halogenation of Benzene

33. © 2011 Pearson Education, Inc. 32 Lewis acid weakens the Br–Br (or Cl–Cl) bond, which makes the halogen a better electrophile:

34. Mechanism for bromination: The catalyst is regenerated: B: Bromide or Benzene 33 © 2011 Pearson Education, Inc.

35. 34

36. © 2011 Pearson Education, Inc. 35 Nitration of Benzene

37. © 2011 Pearson Education, Inc. 36 Nitronium ion formation: Electrophilic aromatic substitution:

38. © 2011 Pearson Education, Inc. 37 Sulfonation of Benzene

39. © 2011 Pearson Education, Inc. 38 Sulfonic acid is a strong acid:

40. © 2011 Pearson Education, Inc. 39 Sulfonation is reversible:

41. © 2011 Pearson Education, Inc. 40 Reaction coordinate diagram for electrophilic aromatic substitution:

42. © 2011 Pearson Education, Inc. 41 Friedel–Crafts Acylation Reactions The electrophile is an acylium ion:

43. © 2011 Pearson Education, Inc. 42 Mechanism for Friedel–Crafts acylation: Must be carried out with more than one equivalent of AlCl 3 :

44. © 2011 Pearson Education, Inc. 43 Friedel–Crafts Alkylation of Benzene

45. © 2011 Pearson Education, Inc. 44 Mechanism for Friedel–Crafts alkylation:

46. © 2011 Pearson Education, Inc. 45 The carbocation will rearrange to a more stable species:

47. © 2011 Pearson Education, Inc. 46 However, 100% of the 2-methyl-2-phenylbutane product can be obtained if a bulky alkyl halide is used:

48. © 2011 Pearson Education, Inc. 47

49. © 2011 Pearson Education, Inc. 48 Friedel–Crafts alkylation will not produce a good yield of an alkylbenzene containing a straight-chain group, because the carbocation will rearrange: Acylium ions, however, do not rearrange:

50. © 2011 Pearson Education, Inc. 49 Methodologies Used for the Reduction Step

51. © 2011 Pearson Education, Inc. 50 Using Coupling Reactions to Alkylate Benzene The Gilman reagent: The Stille reaction:

52. © 2011 Pearson Education, Inc. 51 The Suzuki reaction:

53. © 2011 Pearson Education, Inc. 52 One needs to consider an alternative if another functional group is present in the compound:

54. © 2011 Pearson Education, Inc. 53 Chemical Modification of Substituents of Benzene Reactions of alkyl substituents:

55. © 2011 Pearson Education, Inc. 54 The resulting halide product can undergo a nucleophilic substitution reaction:

56. © 2011 Pearson Education, Inc. 55 Remember that halo-substituted alkyl groups can also undergo E2 and E1 reactions (Section 9.8)

57. © 2011 Pearson Education, Inc. 56 Substitutions with double and triple bonds can undergo catalytic hydrogenation (Sections 4.11 and 6.9)

58. © 2011 Pearson Education, Inc. 57

59. © 2011 Pearson Education, Inc. 58 Oxidation of an alkyl group bonded to a benzene ring… Provided that a hydrogen is bonded to the benzylic carbon,

60. © 2011 Pearson Education, Inc. 59 The same reagent that oxidizes alkyl substituents will oxidize benzylic alcohols:

61. © 2011 Pearson Education, Inc. 60 However, aldehydes or ketones can be generated if a milder oxidizing agent is used:

62. © 2011 Pearson Education, Inc. 61 Reducing a Nitro Substituent

63. © 2011 Pearson Education, Inc. 62 It is possible to selectively reduce just one of the two nitro groups:

64. © 2011 Pearson Education, Inc. 63 Summary of Electrophilic Aromatic Substitution Reactions

65. © 2011 Pearson Education, Inc. 64 Summary of Friedel–Crafts Reactions