1. Problem Review from Monday C H 3 C H C H 3 3 C H C l C H 3 3 A l C l 3 O C H 3 Multiple Additions may be a problem You may get lots of ortho to throw away C l A l C l 3 Problem C H 3 C H C H O 3 3 H H Zn(Hg) + H H Would it help to change the order? HCl O

2. O O O O C H C H C l 3 C l 3 + A l C l 3 A l C l 3 C H 3 Deactivating group. No Friedel Crafts Z n ( H g ) H C l C H C l 3 A l C l 3 O Z n ( H g ) C H H C l 3 C H 3 C H 3

3. O O H C l O O A l C l 3 Predict the main product O O O O O O A B C D E F O O O O O O

4. O O H C l O O A l C l 3 O H O O O

5. O O H C l O O A l C l 3 Predict the main product O O O O O O A B C D E F O O O O O O

6. H + H - F F Draw a mechanism and predict the product F F A B C D E F G F F

7. Review from Monday Electrophilic Aromatic Substitution Reactions C H C H C H C H 3 3 B r 3 3 B r B r - B r B r H B r / F e B r 2 3 + + + B r - F e B r 3 B r B r F e B r 3 60% 39% <1%

8. Review from Monday C H C H C H 3 3 3 B r B r B r H H H C H C H C H C H 3 3 3 3 B r B r / F e B r Methyl does not help meta 2 3 + + Methyl helps stabilize ortho H B r C H 2 B r B r H (and para) para 60% 39% <1%

9. Electron Donating Groups d- d- Most basic sites d- C H 3 Electron Withdrawing Groups d+ d+ Most basic sites d+

10. para ortho d- d- O C H d+ 3 d+ O C H C Bad 3 C B r / F e B r 2 3 slower B r m a i n p r o d u c t Avoids putting d+ near d- d+ Meta wins

11. Electrophilic Aromatic Substitution Reactions B r B r B r - B r / H + B r - F e B r 3 Two more C l - C l / A l C l 3 F e B r 3 C l N O S O H 2 3 O C H - C l / A l C l 3 3 C H C l 3 A l C l 3 C H 3 O Friedel Crafts Alkylation C C H 3 Friedel Crafts Acylation

12. O O N O O / H S O H N O H N O 2 4 3 no reaction N - H O Electrophilic Aromatic Subsitution How can you make HNO3 a stronger acid? Add another acid. O H N O O O O O O N H H N S H S O O O O O O O O O N i t r o n i u m i o n H H

13. O O S O H 3 O Fuming S H S O H 2 4 no reaction O S O O Electrophilic Aromatic Subsitution How can you make H2SO4 a stronger acid? Add another acid. O O O + - H O + H S O + H S S H S 3 4 O O O O O O O H O H

14. Now that we have all our reactions, lets summarize activation and deactivation Electron Donating Groups activate the ring Best O H C C H 3 3 C H N H N H N 3 2 Which one is not a EDG? A B C D C H O 3 H H C O O 3 O O H C O 3 Direct substitution ortho/para E F G H

15. Now that we have all our reactions, lets summarize activation and deactivation Electron Withdrawing Groups deactivate the ring Best H N O O O O N H N H 3 2 C S O H N 3 + H anilinium aniline C H C H 3 3 H O R O O O H N O • EDG or • EWG ? Direct substitution meta

16. O O O H O O O O O H O p k = 9 . 9 9 a O H N N O O O O O O H C H C 3 3 p k = 7 . 1 5 p k = 1 0 . 2 1 a a Predict pKa N O O A. less than 10 B. greater than 10

17. -X pKa -H -NO2 -OCH3 -CH3 -CN -COCH3 -CF3 -F -Cl 9.99 7.15 10.21 X X O H O 10.26 8.61 8.05 d- 8.68 inductive effect resonance effect 9.89 9.41

18. C l What about a halide? Does a Cl activate or deactivate the ring? d- C l C l C l C l d+ inductive effect resonance effect Cl poor at p bonding Deactivates,but directs ortho-para