Organic Chemistry Reviews Chapter 15 Cindy Boulton March 29, 2009

Electrophilic Aromatic Substitution  Hydrogen on Benzene ring is replaced or substituted by an elctrophile  General Mechanism:  Benzene ring acts as nucleophile or Lewis base  Electrophile has a positive charge or a Lewis acid  Pair of electrons from double bond in benzene ring reacts with the electrophile  Forms a Arenium Cation Intermediate, not very stable, with both the electrophile and a Hydrogen attached to a Carbon in the benzene ring  Base already present in solution with a pair of electrons is used to remove the Hydrogen and reform the benzene ring

Electrophilic Aromatic Substitution  Reaction Coordinate  Two humps  Large initial Activation Energy  Intermediate is formed  Small second Activation Energy

Field Crafts Alkylation  Alkyl group is added to a benzene ring  Reactants:  Alkyl halide (R-Cl)  Chloride is the best leaving group  Lewis Acid Catalyst  M-Cl 3 (M: Fe, Al, B)  Electorphile Generation  The Lewis acid is electron deficient and is used to remove the Chloride and generate the carbocation/electrophile (R + ) and the base (M-Cl 4 )  The carbocation can undergo skeletal rearrangement  Attack  The carbocation/electrophile attacks the benzene ring and the base removes the Hydrogen forming H-Cl and regenerating the Lewis Acid catalyst

Field Crafts Acylation  Acyl group (aldehyde or ketone) is added to a benzene ring  Reactants:  Acyl halide (R-(C=O)-Cl)  Chloride is the best leaving group  Lewis Acid Catalyst  M-Cl 3 (M: Fe, Al, B)  Electorphile Generation  The Lewis acid is electron deficient and is used to remove the Chloride and generate the electrophile (R-(C=O) + ) and the base (M- Cl 4 )  Attack  The electrophile attacks the benzene ring and the base removes the Hydrogen forming H-Cl and regenerating the Lewis Acid catalyst

Field Crafts Halogenation  Halogen is added to a benzene ring  Reactants:  Halogen (X 2 )  Lewis Acid Catalyst  M-X 3 (M: Fe, Al, B) (X: Cl, Br, I, difficult with F)  Lewis Acid has to have the same Halogen  Electorphile Generation  The Lewis acid is electron deficient and is used to remove the Chloride and generate the electrophile (X + ) and the base (M-X 4 )  Attack  The electrophile attacks the benzene ring and the base removes the Hydrogen forming H-Cl and regenerating the Lewis Acid catalyst

Field Crafts Sulfonation  Sulfate is added to a benzene ring  Reactants:  Sulfuric Acid  No Lewis Acid Catalyst  Electorphile Generation  Sulfuric Acid generates water and sulfate which acts as the electrophile and the intramolecular base  Attack  The electrophile attacks the benzene ring and then acts as an intermolecular base by removing the Hydrogen and adding it to the Oxygen bonded to the Sulfur with a single bond

Field Crafts Nitration  Nitrite is added to a benzene ring  Reactants:  Nitric Acid and Sulfuric Acid  No Lewis Acid Catalyst  Electorphile Generation  Sulfuric Acid reacts with Nitric Acid to generate nitrite which acts as the electrophile and water which acts as the base  Attack  The electrophile attacks the benzene ring forming Zwitterion and then water removes the hydrogen forming nitrobenzene

Electrophilic Aromatic Substitution of Substituted Benzene  Electron Donating Groups  Activators  Ortho/Para Directors  Increase the rate of the reaction by donating electron density  Electron Withdrawing Groups  Deactivators  Meta Director  Decrease the rate of the reaction by removing electron density

Electrophilic Aromatic Substitution of Substituted Benzene  Electron Groups with Lone Pairs  Activators  Ortho/Para Directors  Increase the rate of the reaction by removing electron density  Halogens  Deactivators  Ortho/Para Directors  Decrease the rate of the reaction by removing electron density

Electrophilic Aromatic Substitution of Substituted Benzene  Mechanism NOT dependent on Electrophile but on group already present  Electron Donating Group  Ortho:  The Arenium Cation Intermediate is formed and is stable  Tertiary Carbocation can be formed with electron density donated – Inductive Effect  Meta:  The Arenium Cation Intermediate cannot form a tertiary carbocation, the positive charge is never on the ipso Carbon  High Activation Energy  Para:  Carbocation on tertiary, ipso Carbon  Ortho and Para have same electronics by differ in sterics. They have the same activation energy, but lower than meta.  Arenium Cation Intermediate forms a resonance hybrid with partial positive charges in a horseshoe shape

Electrophilic Aromatic Substitution of Substituted Benzene  Electron Withdrawing Group  Inductive Effect  Ortho/Para resonance hybrids are destablized with the electron withdrawing group, raising the activation energy  Meta does not lower activation energy, but is the best by default  Group with Lone Pairs  Ortho/Para resonance hybrids can form a 4 th resonance structure  Halogen  Ortho/Para resonance hybrids can form a 4 th resonance structure  Deactivator by inductive effect because it is an electron withdrawing group