Reaction of Benzene and its Derivatives

1. Reaction of Benzene and its Derivatives

2. Reactions of Benzene • Substitution at a ring carbon.

3. Reactions of Benzene Friedel Crafts Friedel Crafts

4. Electrophilic Aromatic Substitution • Electrophilic aromatic substitution: • We study several common electrophiles • how each is generated. • the mechanism by which each replaces hydrogen.

5. EAS: General Mechanism • A general mechanism • General question: What are the electrophiles and how are they generated? Look at particular reactions.

6. Chlorination Step 1: Generation of the electrophile: a chloronium ion. Step 2: Attack of the chloronium ion on the ring.

7. Chlorination Step 3: Proton ejection regenerates the aromatic character of the ring.

8. Nitration (Nitric and Sulfuric Acids) • Generation of the nitronium ion, NO2+ • Step 1: Proton transfer to nitric acid. • Step 2: Loss of H2O gives the nitronium ion, a very strong electrophile. Dehydrated nitric acid.

9. Nitration, Attack of electrophile as before….. Step 1: Attack of the nitronium ion) on the aromatic ring. Step 2: Proton transfer regenerates the aromatic ring.

10. Friedel-Crafts Alkylation Step 1: Formation of an alkyl cation as an ion pair. Step 2: Attack of the alkyl cation. Step 3: Proton transfer regenerates the aromatic ring.

11. Friedel-Crafts Alkylation • There are two major limitations on Friedel-Crafts alkylations: 1. Carbocation rearrangements are common

12. Friedel-Crafts Alkylation 2. F-C alkylation fails on benzene rings bearing one or more of these strongly electron-withdrawing groups.

13. Friedel-Crafts Acylation • Friedel-Crafts acylation forms a new C-C bond between a benzene ring and an acyl group.

14. Friedel-Crafts Acylation • The electrophile is an acylium ion.

15. Friedel-Crafts Acylation • An acylium ion is represented as a resonance hybrid of two major contributing structures. • Friedel-Crafts acylations are free of major limitation of Friedel-Crafts alkylations; acylium ions do not rearrange, do not polyacylate (why?), do not rearrange.

16. Synthesis, Friedel-Crafts Acylation • preparation of unrearranged alkylbenzenes. What else could be used here?

17. Other Aromatic Alkylations • Carbocations are generated by • treatment of an alkene with a proton acid, most commonly H2SO4, H3PO4, or HF/BF3. • and by treating an alcohol with H2SO4 or H3PO4.

19. Di- and Polysubstitution • Orientation on nitration of monosubstituted benzenes. Favor ortho/para substitution Favor ortho/para substitution Favor ortho/para substitution Favor meta substitution

20. Directivity of substituents

21. Di- and Polysubstitution • Two ways to characterize the substituent • Orientation: • Some substituents direct preferentially to ortho & para positions; others to meta positions. • Substituents are classified as either ortho-para directingor meta directing toward further substitution. • Rate • Some substituents cause the rate of a second substitution to be greater than that for benzene itself; others cause the rate to be lower. • Substituents are classified as activating or deactivating toward further substitution.

22. Di- and Polysubstitution • -OCH3 is ortho-para directing. • -COOH is meta directing.

23. Di- and Polysubstitution Recall the polysubstitution in FC alkylation.

24. Di- and Polysubstitution • Generalizations: • Directivity: Alkyl, phenyl, and all substituents in which the atom bonded to the ring has an unshared pair of electrons are ortho-para directing. All other substituents are meta directing. • Activation: All ortho-para directing groups except the halogens are activating toward further substitution. The halogens are weakly deactivating.

25. Di- and Polysubstitution • The order of steps is important.