Electrophilic Aromatic Substitution

1. => Electrophilic Aromatic Substitution Electrophile substitutes for a hydrogen on the benzene ring. Chapter 17

2. Mechanism => Chapter 17

3. Energy Diagramfor Bromination => Chapter 17

4. Bromination of Benzene • Requires a stronger electrophile than Br2. • Use a strong Lewis acid catalyst, FeBr3. Chapter 17

5. => Chlorination and Iodination • Chlorination is similar to bromination. Use AlCl3 as the Lewis acid catalyst. • Iodination requires an acidic oxidizing agent, like nitric acid, which oxidizes the iodine to an iodonium ion. Chapter 17

6. Nitration of Benzene Use sulfuric acid with nitric acid to form the nitronium ion electrophile. NO2+ then forms a sigma complex with benzene, loses H+ to form nitrobenzene. => Chapter 17

7. => Sulfonation Sulfur trioxide, SO3, in fuming sulfuric acid is the electrophile. Chapter 17

8. => Benzene-d6 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. Chapter 17

9. => Nitration of Toluene • Toluene reacts 25 times faster than benzene. The methyl group is an activator. • The product mix contains mostly ortho and para substituted molecules. Chapter 17

10. Sigma Complex Intermediate is more stable if nitration occurs at the orthoor para position. => Chapter 17

11. Energy Diagram => Chapter 17

12. => Activating, O-, P-Directing Substituents • Alkyl groups stabilize the sigma complex by induction, donating electron density through the sigma bond. • Substituents with a lone pair of electrons stabilize the sigma complex by resonance. Chapter 17

13. NITRATION OF ANISOLE

14. Nitration of Anisole ortho meta para activated ring actual products para ortho +

15. : ortho EXTRA! meta : para EXTRA!

16. RECALL: HAMMOND POSTULATE Ea Energy Profiles NITRATION OF ANISOLE benzenium intermediate meta benzenium intermediates have more resonance ortho para ortho-para director

17. BENZENIUM IONS GIVE ELIMINATION INSTEAD OF ADDITION ADDITION REACTION doesn’t happen resonance would be lost X ELIMINATION REACTION restores aromatic ring resonance ( 36 Kcal / mole )

18. => The Amino Group Aniline reacts with bromine water (without a catalyst) to yield the tribromide. Sodium bicarbonate is added to neutralize the HBr that’s also formed. Chapter 17

19. Summary ofActivators => Chapter 17

20. Deactivating Meta-Directing Substituents • Electrophilic substitution reactions for nitrobenzene are 100,000 times slower than for benzene. • The product mix contains mostly the meta isomer, only small amounts of the orthoand para isomers. • Meta-directors deactivate all positions on the ring, but the meta position is less deactivated. => Chapter 17

21. Ortho Substitutionon Nitrobenzene => Chapter 17

22. Para Substitution on Nitrobenzene => Chapter 17

23. Meta Substitutionon Nitrobenzene => Chapter 17

24. Energy Diagram => Chapter 17

25. Structure of Meta-Directing Deactivators • The atom attached to the aromatic ring will have a partial positive charge. • Electron density is withdrawn inductively along the sigma bond, so the ring is less electron-rich than benzene. => Chapter 17

26. Summary of Deactivators => Chapter 17

27. More Deactivators => Chapter 17

28. Halobenzenes • Halogens are deactivating toward electrophilic substitution, but are ortho, para-directing! • Since halogens are very electronegative, they withdraw electron density from the ring inductively along the sigma bond. • But halogens have lone pairs of electrons that can stabilize the sigma complex by resonance. => Chapter 17

29. Ortho and para attacks produce a bromonium ionand other resonance structures. No bromonium ion possible with meta attack. => Sigma Complexfor Bromobenzene Chapter 17

30. Energy Diagram => Chapter 17

31. Summary of Directing Effects => Chapter 17

32. DIRECTIVITY OF SINGLE GROUPS

33. ortho, para - Directing Groups Groups that donate electron density to the ring. PROFILE: : E+ increased reactivity +I Substituent +R Substituent .. These groups also “activate” the ring, or make it more reactive. CH3-O- .. CH3- .. R- CH3-N- .. -NH2 .. The +R groups activate the ring more strongly than +I groups. -O-H ..

34. meta - Directing Groups Groups that withdraw electron density from the ring. PROFILE: d+ d- E+ decreased reactivity -I Substituent -R Substituent These groups also “deactivate” the ring, or make it less reactive. + + - -SO3H

35. THE EXCEPTION Halides - o,p Directors / Deactivating Halides represent a special case: .. : : They are o,p directing groups that are deactivating E+ They are o,p directors (+R effect ) They are deactivating ( -I effect ) Most other other substituents fall into one of these four categories: +R / -I / o,p / deactivating 1) +R / o,p / activating -F -Cl -Br -I 2) +I / o,p / activating 3) -R / m / deactivating 4) -I / m / deactivating

36. PREDICT ! o,p m o,p m

37. DIRECTIVITY OF MULTIPLE GROUPS

38. GROUPS ACTING IN CONCERT steric crowding o,p director m-director very little formed HNO3 H2SO4 When groups direct to the same positions it is easy to predict the product. major product

39. GROUPS COMPETING o,p-directing groups win over m-directing groups too crowded X HNO3 + H2SO4

40. RESONANCE VERSUS INDUCTIVE EFFECT +R HNO3 H2SO4 major product +I resonance effects are more important than inductive effects

41. SOME GENERAL RULES 1) Activating (o,p) groups (+R, +I) win over deactivating (m) groups (-R,-I). 2) Resonance groups (+R) win over inductive (+I) groups. 3) 1,2,3-Trisubstituted products rarely form due to excessive steric crowding. 4) With bulky directing groups, there will usually be more p-substitution than o-substitution. 5) The incoming group replaces a hydrogen, it will not usually displace a substituent already in place.

42. HOW CAN YOU MAKE ... only, no para

43. BROMINE - WATER REAGENT PHENOLS AND ANILINES

44. BROMINE IN WATER This reagent works only with highly-activated rings such as phenols, anisoles and anilines. .. .. .. .. .. .. - : : : : : .. .. .. .. + .. .. : + .. + bromonium ion etc

45. PHENOLS AND ANILINES REACT Br2 H2O All available positions are bromiated. Br2 H2O

46. Friedel-Crafts Alkylation • Synthesis of alkyl benzenes from alkyl halides and a Lewis acid, usually AlCl3. • Reactions of alkyl halide with Lewis acid produces a carbocation which is the electrophile. • Other sources of carbocations: alkenes + HF or alcohols + BF3. => Chapter 17

47. => Examples ofCarbocation Formation Chapter 17

48. - + => Formation of Alkyl Benzene Chapter 17

49. Limitations ofFriedel-Crafts • Reaction fails if benzene has a substituent that is more deactivating than halogen. • Carbocations rearrange. Reaction of benzene with n-propyl chloride and AlCl3 produces isopropylbenzene. • The alkylbenzene product is more reactive than benzene, so polyalkylation occurs. => Chapter 17

50. Friedel-CraftsAcylation • Acyl chloride is used in place of alkyl chloride. • The acylium ion intermediate is resonance stabilized and does not rearrange like a carbocation. • The product is a phenyl ketone that is less reactive than benzene. => Chapter 17