12.12 Substituent Effects in Electrophilic Aromatic Substitution: Activating Substituents

1. 12.12Substituent Effects in ElectrophilicAromatic Substitution:Activating Substituents

2. Table 12.2 • Classification of Substituents in Electrophilic Aromatic Substitution Reactions Very strongly activating Strongly activating Activating Standard of comparison is H Deactivating Strongly deactivating Very strongly deactivating

3. Generalizations 1. All activating substituents are ortho-para directors. 2. Halogen substituents are slightly deactivating but ortho-para directing. 3. Strongly deactivating substituents are meta directors.

4. Electron-Releasing Groups (ERGs) are ortho-para directing and activating ERG ERGs include —R, —Ar, and —C=C

5. Electron-Releasing Groups (ERGs) are ortho-para directing and strongly activating ERG ERGs such as —OH, and —OR arestrongly activating

6. OH OH OH NO2 NO2 Nitration of Phenol occurs about 1000 times faster than nitration of benzene HNO3 + 44% 56%

7. OCH3 OCH3 Br Bromination of Anisole FeBr3 catalyst not necessary Br2 aceticacid 90%

8. •• •• • • + OCH3 OCH3 OCH3 • • H H H H + + H H H H Br Br H H Oxygen Lone Pair Stabilizes Intermediate •• all atomshave octets H H H H Br H

9. • • Electron-Releasing Groups (ERGs) ERG ERGs with a lone pair on the atom directlyattached to the ring are ortho-para directingand strongly activating

10. O •• •• •• • • • • ERG = • OH OR OCR • • • O • • • • NH2 NHR NR2 NHCR • • • • Examples All of these are ortho-para directingand strongly to very strongly activating

11. + + ERG ERG H H H H X H H H H X H H Lone Pair Stabilizes Intermediates forortho and para Substitution comparable stabilization not possible for intermediate leading to meta substitution

12. 12.13Substituent Effects in ElectrophilicAromatic Substitution:Strongly Deactivating Substituents

13. • • ERG ERG • • X H H H + + H H H H H X H H ERGs Stabilize Intermediates forortho and para Substitution

14. Electron-withdrawing Groups (EWGs) DestabilizeIntermediates for ortho and para Substitution —CF3 is a powerful EWG. It is strongly deactivating and meta directing EWG EWG X H H H + + H H H H H X H H

15. O O —CH —CR O O —COH —COR O —CCl Many EWGs Have a Carbonyl GroupAttached Directly to the Ring All of these are meta directing and strongly deactivating —EWG =

16. —C N Other EWGs Include: All of these are meta directing and strongly deactivating —EWG = —NO2 —SO3H

17. O2N O O CH CH Nitration of Benzaldehyde HNO3 H2SO4 75-84%

18. O O CCl CCl Problem 12.14(a); page 468 Cl Cl2 FeCl3 62%

19. Disulfonation of Benzene HO3S SO3 SO3H H2SO4 90%

20. Bromination of Nitrobenzene Br Br2 NO2 NO2 Fe 60-75%

21. 12.14Substituent Effects in ElectrophilicAromatic Substitution:Halogens F, Cl, Br, and I are ortho-para directing,but deactivating

22. Cl Cl Cl Cl NO2 NO2 NO2 Nitration of Chlorobenzene The rate of nitration of chlorobenzene is about 30 times slower than that of benzene. HNO3 + + H2SO4 30% 1% 69%

23. CH3 42 42 2.5 2.5 58 Nitration of Toluene vs. Chlorobenzene Cl 0.029 0.029 0.009 0.009 0.137