Organic Chemistry Reviews Chapter 15

1. Organic Chemistry ReviewsChapter 15 Cindy Boulton March 29, 2009

2. 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 AreniumCation 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

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

4. 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-Cl3 (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-Cl4) • 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

5. 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-Cl3 (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-Cl4) • Attack • The electrophile attacks the benzene ring and the base removes the Hydrogen forming H-Cl and regenerating the Lewis Acid catalyst

6. Field Crafts Halogenation • Halogen is added to a benzene ring • Reactants: • Halogen (X2) • Lewis Acid Catalyst • M-X3 (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-X4) • Attack • The electrophile attacks the benzene ring and the base removes the Hydrogen forming H-Cl and regenerating the Lewis Acid catalyst

7. 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

8. 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

9. 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

10. 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

11. Electrophilic Aromatic Substitution of Substituted Benzene • Mechanism NOT dependent on Electrophile but on group already present • Electron Donating Group • Ortho: • The AreniumCation Intermediate is formed and is stable • Tertiary Carbocation can be formed with electron density donated – Inductive Effect • Meta: • The AreniumCation 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. • AreniumCation Intermediate forms a resonance hybrid with partial positive charges in a horseshoe shape

12. 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 4th resonance structure • Halogen • Ortho/Para resonance hybrids can form a 4th resonance structure • Deactivator by inductive effect because it is an electron withdrawing group