Reaction of Benzene and its Derivatives

Reactions of Benzene Substitution at a ring carbon.

Reactions of Benzene Friedel Crafts Friedel Crafts

Electrophilic Aromatic Substitution We study several common electrophiles how each is generated. the mechanism by which each replaces hydrogen.

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

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

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

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.

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.

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.

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

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

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

Friedel-Crafts Acylation The electrophile is an acylium ion.

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.

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

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.

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  

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

Directivity of substituents

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.

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

Di- and Polysubstitution Recall the polysubstitution in FC alkylation.

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.

Di- and Polysubstitution The order of steps is important.