Chapter 4. AROMATIC ELECTROPHILIC SUBSTITUTION REACTIONS

1. Chapter 4. AROMATIC ELECTROPHILIC SUBSTITUTION REACTIONS Objectives: Identify the reactants and products; Describe and explain the mechanism and the influential factors of addition reactions on aromatic compounds.

2. 4.1. Introduction Definition: AES = Replacement of one of the H on an aromatic ring by an electrophile Substrates = Aromatic rings. Reaction sites: C=C bonds on the ring. Characteristic of rxn sites: presence of pi-electrons which attract electrophiles Reagents: electrophiles seeking to bind with the pi-electrons. Most electrophiles are generated in situ using Lewis acids. Ex: Br2 + FeBr3 --> Br(+) + FeBr4(-) Result: formation of a substituted aromatic compound Substitution occurs instead of addition on the intermediate because of the additional stability gained by forming an aromatic ring.

3. AROMATIC ELECTROPHILIC SUBSTITUTION (General Pathway)

4. 4.2. Overview of Aromatic� Electrophilic Substitution Reactions a. Halogenation Substrates: aromatic rings. Reaction sites: C=C bonds on the ring. Reagents: Halogens with a (+) charge. Example: Br(+), generated from reaction between Br2 and FeBr3 (a Lewis acid). Result: Brominated aromatic rings Other similar AES reactions: Fluorination, chlorination & iodination (using F2, Cl2 and I2 in presence of Lewis acids such as FeBr3)

5. Halogenation of Aromatic Rings ( Example)

6. b. Nitration Substrates: aromatic rings. Reaction sites: C=C bonds on the ring. Reagent: NO2(+) (nitronium ion), electrophile, generated using using HNO3 in H2SO4 (as Lewis acid) Products: aromatic nitro compounds. Note: Incorporation of a nitro group makes further AES reactions more difficult

7. Nitration (Illustration)

8. c. Sulfonation Substrates: aromatic rings. Reaction sites: C=C bonds on the ring. Reagent: �HSO3(+) (sulfonium): Electrophile, produced using H2SO4 / SO3 (FUMING SULFURIC ACID) �Products: aromatic sulfonic acids Note: Sulfonation deactivates the ring against further AES reactions

9. Sulfonation (Illustration)

10. d. Alkylation (aka Friedel-Crafts Alkylation) Substrate: aromatic ring. Reaction sites: C=C bonds on the ring. Reagents: alkyl carbocations (R(+), electrophiles), generated using alkyl halides w/ Lewis acid catalysts (mostly AlCl3). Products: Alkylated aromatic compounds Notes: *Alkyl cations rearrange to more stable ions * Alkylation activates the rings for further AES reactions

11. Friedel-Crafts Alkylation (Illustration)

12. e. Acylation Substrate: aromatic ring. Reaction sites: C=C bonds on the ring. Reagents: R-CO(+), aka acyl ions, electrophile, prepared reaction of acyl halide (R-CO-X) and a Lewis acid (AlCl3 mostly) Products: Acylated aromatic compounds Notes: * Acyl ions do not rearrange * Acylation deactivates rings against further AES reactions

13. Acylation (Illustration)

14. 4.3. Substituent effects on AES (Thought Teaser)

15. 4.3. Substituent effects on AES a. Electron Donating (ED) Substitutents. Case: atoms with lone pairs of electrons directly attached to the ring. Example: H-O-, CH3-O-, H2N-, (CH3)2N-, ... Other examples: see pg 762 Role: ED substituents donate electrons to ortho and para positions of the aromatic ring that they are attached to and make them more reactive. Result: ED substituents direct electrophiles to bind to ortho and para positions preferentially.

16. ED Substitutents Effect on AES (Examples)

17. Inductive ED Substituents Case: Alkyl groups. C atoms withdraw electrons from the H�s to which they are bound. Those C�s are electron-rich Role: they donate electron density (similar to electric field) instead of electron pairs to aromatic rings. Result: inductive ED substituents make aromatic rings more reactive to electrophiles. Consequence: inductive ED direct electrophiles to ortho and para positions

18. Inductive ED Substituents Effect on AES (Example)

19. Substituent effects on AES (Thought Teaser 2)

20. b. Electron Withdrawing (EW) Substitutents. Case: C=O, NO2, SO2, � groups directly attached to the aromatic ring. Examples: CH3-CO-, HSO3-, NO2-... Other examples: see pg 766 Role: EW substituents withdraw electrons from ortho and para positions of the aromatic ring that they are attached to and make those position less reactive. Result: EW substituents direct electrophiles to bind to meta positions preferentially.

21. EW Substitutents Effect on AES (Examples)

22. Deactivating and Ortho and Para Directing Substituents Case: halogens. More electronegative than C and have lone pairs of electrons Characteristics: * Inductively Electron-withdrawing by electronegativity. * Electron-donating using lone pairs Overall result: ED property prevails. Consequence: halogens direct electrophiles to ortho and para positions on aromatic rings

23. Halogen Effect on AES (Example)

24. c. Presence of ED and EW substituents on the same ring. When ED and EW substituents are found on the same ring, ED subs outweigh the EW subs. Classification of substituents from strongest to weakest: 1. Ortho and para directors that donate electrons using lone pairs 2. Inductive ortho and para directors. 3. Meta directors� Example: see pg 770