1. CHEMISTRY OF BENZENE: ELECTROPHILIC AROMATIC SUBSTITUTION Dr. Sheppard CHEM 2412 Summer 2015 Klein (2 nd ed.) sections: 19.1, 19.2, 19.3, 19.4, 19.5, 19.6, 18.6, 19.7, 19.8, 19.9, 19.10, 19.11, 19.12

2. Benzene Reactivity Unsaturated, but doesn’t behave like alkene Alkenes: Benzene: Reaction is called electrophilic aromatic substitution

3. Reactions of Aromatic Compounds I. Electrophilic aromatic substitution mechanism II. Halogenation III. Sulfonation IV. Nitration V. Friedel-Crafts Alkylation and Acylation VI. Reactions of Benzene Substituents VII. EAS on Substituted Benzenes VIII. Synthesis

4. Electrophilic Aromatic Substitution Aromatic ring (nucleophile) + electrophile

5. Electrophilic Aromatic Substitution Mechanism:

6. Halogenation Reagents X 2 Br 2 or Cl 2 F 2 too reactive, I 2 needs additional reagents FeX 3 or AlX 3 Catalyst Makes X 2 more electrophilic Example: bromination

7. Halogenation Mechanism

8. Energy Diagram Aromatic (substitution) product is more stable than product from addition across double bond See benzene worksheet questions 1-19

9. SO 3 and H 2 SO 4 = “fuming sulfuric acid” Electrophile = SO 3 or HSO 3 + Sulfonic acid can be converted into phenol Not covered in Klein Sulfonation

10. Electrophile = nitronium ion (NO 2 + ) Nitration

11. Nitro group can be reduced to amine Reagents: 1. SnCl 2, Zn, or Fe and H + H 2, metal catalyst Will also reduce C≡C, C=C, but not benzene Nitration

12. Friedel-Crafts Alkylation New carbon-carbon bond between benzene and R group Example: Catalyst makes RX a better electrophile (~R + )

13. Limitations to Friedel-Crafts Alkylation 1. RX structure X = Cl, Br, I R = alkyl (not aryl or vinylic)

14. Limitations to Friedel-Crafts Alkylation 2. Reaction fails on benzenes substituted with electron- withdrawing groups (EWGs) These groups remove electron-density from the benzene ring (make the nucleophile less nucleophilic) 3. Reaction fails on benzenes substituted with amino groups These groups can react with the catalyst These groups can become protonated and form –NH 3 + (EWG)

15. Limitations to Friedel-Crafts Alkylation 4. Multiple substitution can occur Polyalkylation

16. Limitations to Friedel-Crafts Alkylation 5. Rearrangements can occur Electrophile is ~R +, so can rearrange to make a more stable R +

17. Example Draw the product of the F-C alkylation reaction of benzene with 1-chloro-2-methylpropane (using the appropriate catalyst)

18. New carbon-carbon bond between benzene and acyl group Example: Reaction still does not work with EWG or amine No polyalkylation Reaction only occurs once because product contains EWG No rearrangements Acyl cation stabilized by resonance Friedel-Crafts Acylation

19. Example Aryl ketones can be reduced to form alkyl benzenes This alkyl benzene cannot be made from F-C alkylation Rearrangement Reducing agents H 2, metal catalyst Will also reduce C=C, C≡C, NO 2 Zn(Hg), HCl (Clemmensen reduction)

20. Reactions of Benzene Substituents Already seen in this chapter: 1. ─NO 2 → ─NH 2 2. ─SO 3 H → ─OH 3. ─C(O)R → ─CH 2 R Additional reactions: 4. Oxidation with KMnO 4 or H 2 CrO 4

21. Additional reactions: 5. Halogenation Forms alkyl halide, which can undergo further substitution or elimination Reaction occurs at benzylic position Most stable radical intermediate Reactions of Benzene Substituents

22. Summary of Reactions

23. Propose a synthesis for the following compound, using benzene as the starting material.

24. Is it possible to synthesize propylbenzene using a Friedel-Crafts alkylation? Explain.

25. Propose an alternate synthesis for propylbenzene from benzene.

26. The following conversion requires more than one step. Show reagents and experimental conditions necessary to bring about this conversion.