Reactions of aromatic compounds

1. Reactions of aromatic compounds

2. Aromatic substitution: the basics Most common reaction which occurs for aromatic compounds Benzene ring serves as a Lewis base, since it is electron-rich Site of electron density on the benzene ring is based on its six pi electrons Overall reaction is the substitution of an electrophile (E+) for a proton (H+) on the aromatic ring

3. Electrophilic aromatic substitution Types of substitution reactions halogenation Nitration Sulfonation/desulfonation Friedel-Crafts alkylation/acylation

4. Halogenation Utilizes halogen (chlorine, bromine, or iodine) in the presence of a Lewis acid catalyst The catalyst makes the halogen atom more eletrophilic, producing a species that behaves as if it is an electrophile Polarized halogen molecule then attacks the pi electron system of the benzene ring. This yields a sigma complex

5. Bromination occurs in the presence of FeBr3 catalyst Chlorination occurs in the presence of either FeCl3 or AlCl3 catalyst Iodination usually requires a strong oxidizing agent, such as HNO3

6. Nitration Normally occurs in the presence of an oxidizing mixture of nitric and sulfuric acids Sulfuric acid serves as a catalyst in the reaction Nitronium ion (NO2+) is the primary electrophile produced in the reaction

7. Mechanism involves the nitronium ion attacking the electron-rich benzene ring, producing the sigma complex In the end, nitro group substitutes for a H in the benzene ring, producing nitrobenzene

8. Sulfonation Occurs in the presence of �fuming� sulfuric acid, a mixture of H2SO4 and SO3 Electrophile is either SO3 or HSO3+ Sulfonation is reversible Sulfonation is favored in strong acid, but desulfonation occurs in hot, dilute, aqueous acid

9. Substituent effects on the aromatic ring Substituent effects can either activate the ring (making the compound more reactive than benzene) or deactivate the ring (making the compound less reactive than benzene)

10. Types of substituents on the benzene ring Three types of substutents on benzene ring: 1) ortho-para activators 2) ortho-para directing deactivators 3) meta directing deactivators

11. Ortho-para activators Examples include: -NH2, -OH, -OR, -R, NHCOCH3 (acetamido), phenyl These groups allow the resulting compound to be more reactive than benzene itself These substituents allow subsequent substituents in the reaction to orient in the ortho or para position when a disubstituted product is formed

12. With alkyl groups, this effect by ortho-para directing activator is called inductive stabilization, because alkyl group donates electron density through sigma bond joining it with the benzene ring With alkoxy and amino groups, this effect is based on resonance stabilization. On the oxygen or nitrogen atom, it is called resonance-donating or pi donating

13. Meta-directing deactivators These groups tend to deactivate the meta position less than the ortho-para positions, allowing for meta substitution Examples include: -CHO, -COOCH3, -COCH3, SO3H, -CN, NO2.

14. Ortho-para directing deactivators These include the halogens (F, Cl, Br, and I) Halogens are deactivating groups, but they are ortho-para directors Reasons: a) halogens are strongly electronegative b) halogens have nonbonding electrons that can donate electron density through pi bonding

15. Friedel-Crafts reactions Two types of Friedel-Crafts reactions: a) Friedel-Crafts alkylations b) Friedel-Crafts acylations

16. Both Friedel-Crafts reactions are electrophilic substitution reactions Both use a Lewis acid catalyst in the mechanism (usually AlCl3, FeBr3, or FeCl3)

17. Friedel-Crafts alkylation Electrophile is a carbocation AlCl3 catalyzes the reaction in the same manner as halogenation, producing the carbocation Loss of a proton completes the reaction

18. Limitations of the Friedel-Crafts reactions Works only with benzene, activated benzene derivatives (e.g. toluene), and haolbenzene. They fail with strongly deactivated systems, such as nitrobenzene Prone to carbocation rearrangements Since alkyl groups are activating substituents, the product of the Friedel-Crafts alkylation is more reactive than the starting material

19. Friedel-Crafts acylation An acyl group is introduced to the ring, when an aromatic ring reacts with an acid chloride, in the presence of a catalyst Mechanism is very similar to Friedel-Crafts alkyation

20. Friedel-Crafts acylation has some slight advantages over Friedel-Crafts alkylation reactions: 1) Acyl group can be added to the ring only once, because the acylbenzene formed is less reactive than benzene itself 2) Acyl groups do not undergo rearrangements, due to the formation of the stable acylium cation as the electrophile

21. Clemmensen reduction Reaction involves the use amalgamated zinc (Zn-Hg) in the presence of acid Reduces the carbonyl group to an alkane

22. Side chain reactions with benzene Two types of side chain reactions: 1) permanganate oxidation 2) side-chain halogenation

23. Side chain oxidation Potassium permaganate attacks at the benzylic position in order to form benzoic acid and derivatives

24. Side chain halogenation Chlorine or bromine can attack a benzylic hydrogen in the presence of light to produce a a-substituted product

25. Chlorination tends to give mixtures of products, monosubstituted and disubstituted Bromination is more selective than chlorination, since bromine is less reactive than chlorine

26. Addition reactions to the benzene ring Chlorination: Benzene can combine with an excess of chlorine, under heat and pressure, can break the pi bonds in benzene, and give a product called benzene hexachloride Hydrogenation: Catalytic hydrogenation of benzene at elevated temperatures and pressures will produce the cyclohexane product, with very high yields