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
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.

18. Lewis acid+ halogen(X2)
Benzene
Reaction
Halogenation
Sulphonation
Nitration
Friedel Craft
Alkylation
Acylation
Reagent
Lewis acid+ halogen(X2)
(Lewis acid= AlCl3, BF3, HF, H3PO4, FeX3 )
(X2= Cl2 or Br2)
H2SO4 + SO3
HNO3 + H2SO4
Lewis acid + RX
(R=Alkyl)
(X=Cl, Br, OH , CH= CH2)
Lewis acid + RC(O)X
(X=Cl or Br)
Electrophile
Cl+ or Br+
SO3H+
NO3+ R+
RC(O)+
Product

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 directing or 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.