Chapter 18 Reactions of Aromatic molecules

1. Chapter 18 Reactions of Aromatic molecules • Benzene is aromatic: a cyclic conjugated compound with 6  electrons • Reactions of benzene lead to the retention of the aromatic core

2. Types of Reactions • Electrophilic substitution • Diazonium chemistry • Nucleophilic substitution • Misc. modification of substituents

3. Electrophilic Substitution Reactions of Benzene and Its Derivatives

4. Electrophilic Substitution versus addition Arenium ion: Wheland intermediate Also called sigma complex

5. Energy diagram comparison of electrophilic substitution versus electrophilic addition Is this kinetic or thermodynamic control?

6. ElectrophilicBromination of Aromatic Rings toluene para-bromotoluene ortho-bromotoluene meta-bromonitrobenzene Regiochemistry (ortho, para, meta) will depend on relative stability of resonance structures for carbocation intermediates

7. Mechanism for ElectrophilicBromination of Aromatic Rings paracarbocation orthocarbocation orthocarbocation

9. Electrophilic substitution of Bromobenzene

10. Halogens are orthopara directors, but are still deactivating compared with benzene

11. Transformations of Aryl bromides

12. Aromatic Nitration • The combination of nitric acid and sulfuric acid produces NO2+ (nitronium ion) • The reaction with benzene produces nitrobenzene Gun solvent

13. Nitration of toluene: an electron rich monomer

14. ortho & paraRegioselectivity explained Kinetics are more favorable for orthoand paraisomers with electron donating substitutent on benzene

17. Too corrosive for artillery shells • High explosive: Shock wave • Secondary explosive: requires primer (primary explosive) to detonate • Nitroaromatics are harmful: aplastic anemia and liver toxicity

18. Reactions of nitroaromatics • Nitro is deactivating (destabilizes the Wheland intermediate & slows reactions). • Reactions are 100,000 slower than with benzene • Meta directing More polynitration mono-bromination Reduction to anilines and azo compounds Nucleophilic aromatic substitution

19. Meta selective: electron withdrawing groups • electron withdrawing group inductively destabilizes adjacent carbocations in ortho and para cases. • No adjacent carbocation in meta regiochemistry resonance structures

20. Reduction of Nitroaromatics to Aryl amines Amine group is electron donating: changes subsequent regiochemistry from meta to ortho-para

21. Aromatic Sulfonation • Substitution of H by SO3 (sulfonation) • Reaction with a mixture of sulfuric acid and SO3 • Reactive species is sulfur trioxide or its conjugate acid • Reaction occurs via Wheland intermediate and is reversible

22. Alkali Fusion of Aromatic Sulfonic Acids • Sulfonic acids are useful as intermediates • Heating with NaOH at 300 ºC followed by neutralization with acid replaces the SO3H group with an OH • Example is the synthesis of p-cresol

23. Alkylation of Aromatic Rings: The Friedel–Crafts Reaction • Aromatic substitution of a R+ for H • Aluminum chloride promotes the formation of the carbocation • Rearrangement of carbocation can occur

24. Friedel Craft alkylation mechanism

25. Friedel Craft alkylation with rearrangements

26. Limitations of the Friedel-Crafts Alkylation • Only alkyl halides can be used (F, Cl, I, Br) • Aryl halides and vinylic halides do not react (their carbocations are too hard to form) • Will not work with rings containing an amino group substituent or a strongly electron-withdrawing group

27. Control Problems • Multiple alkylations can occur because the first alkylation is activating

28. Acylationof Aromatic Rings • Reaction of an acid chloride (RCOCl) and an aromatic ring in the presence of AlCl3 introduces acyl group, COR • Benzene with acetyl chloride yields acetophenone

29. Friedel Craft Acylation Mechanism

30. Acylation – No rearrangement of acylium ions

32. Ortho- and Para-Directing Deactivators: Halogens • Electron-withdrawing inductive effect outweighs weaker electron-donating resonance effect • Resonance effect is only at the ortho and para positions, stabilizing carbocation intermediate

33. Strongly Activating o,p directors: Multiple additions

34. Reduce reactivity with acetyl groups

35. Summary of activation versus deactivation and ortho& paraversus meta direction

36. With multiple substitutents there can be antagonistic or reinforcing effects Antagonistic or Non-Cooperative Reinforcing or Cooperative D = Electron Donating Group (ortho/para-directing) W = Electron Withdrawing Group (meta-directing)

37. => Multiple Substituents in antagonistic systems The most strongly activating substituent will determine the position of the next substitution. May have mixtures.

39. Sulfonic acid blocking groups

41. ?

42. ?

44. Electrophilic substitution reaction used to make plastics Acid or base catalyzed reactions Bakelite, Novolac Acid catalyzed reaction of phenol with formaldehyde

45. Electrophilic substitution reaction used to make plastics Acid catalyzed reaction of phenol with formaldehyde

46. Electrophilic substitution reaction used to make plastics Base catalyzed reaction of phenol with formaldehyde

47. NucleophilicAromatic Substitution • While protons attached to electron-rich aromatics can be displaced by electrophiles, halogens attached to electron-depleted aromatics can be displaced by nucleophies • Nucleophilic aromatic substitution is similar to SN1/SN2 in its outcome, but followscompletely different mechanisms Substitution Nucleophilic Aromatic (SNAr), the BenzyneMech, and reaction of diazonium salts

48. SNAr Mechanism: Electron EWG’s

49. Addition-Elimination Reactions • Typical for aryl halides with nitro groups in ortho or para position • Addition to form intermediates (Meisenheimer complexes) by electron-withdrawal • Halide ion is then lost by elimination

50. Chlorobenzene is unreactive under ordinary laboratory conditions…