1. Chem 125 Lecture 69 4/17/08 Projected material This material is for the exclusive use of Chem 125 students at Yale and may not be copied or distributed further. It is not readily understood without reference to notes from the lecture.

2. conrotationdisrotation MöbiusHückel 22 11 33 44 55 66 22 11 33 44 55 66  11 22 33 44   11 22 33 44 

3. O2NO2N X O2NO2N XX NO 2 + + Substituent Effects on Rate X NO 2 + (from HONO 2 /H 2 SO 4 ) X Relative Rate (overall) H[1] Cl0.03  donation /  withdrawal CH 3 25 OH1000  (or  ) e-donation eases formation of cation intermediates NO 2 6  10 -8 (CH 3 ) 3 N + 1  10 -8  (or  ) e-withdrawal retards formation of cation intermediates

4. Why is -NO 2 e-Withdrawing when -OH is e-Donating? -NO 2 6  10 -8  e-withdrawal retards formation of cation intermediates -OH1000  e-donation eases N OO O H pCpC  C=C  p O 0 High HOMO; Good Overlap with Phenyl Low OMO; Good Overlap with Phenyl High HOMO; Low LUMO; Good Overlap with Phenyl OH is a  Donor NO 2 is a  Acceptor No Overlap with Phenyl NO 2 is allylic (willing but not able)

5. Substituent Effects on Orientation (p. 763) X NO 2 + (from HONO 2 /H 2 SO 4 ) X NO 2 + + + + H O2NO2N X + + + + H H X + + + X- Relative Rate (per replaceable H) H-[1] Cl-0.00080.030.13 O 2 N- 9  10 -8 0.6  10 -8 0.03  10 -8 H 3 C-13946 (CH 3 ) 3 C-4672 Directing Activating Deactivating Act Deact  (CH 3 ) 3 N- 3  10 -8 0.6  10 -8 + _ orthometapara EtOC=O 0.0060.0006 - 0.003 o/po/p m o/po/p “e-donating” “e-withdrawing” (steric hindrance) ?

6. Preparation Problems NO 2 Cl NO 2 Cl 2 FeCl 3 NO 2 Cl Cl 2 FeCl 3 (Cl + FeCl 4 - ) NH 2 Cl HNO 3 H 2 SO 4 OH Cl “reduction” (Zn/HCl?) H2OH2O 100°C HONO (NaNO 2 /HCl) N2N2 Cl + diazonium salt Cl - or : Hal CN NO 2 H Cl

7. Yale ‘98S

8. Friedel-Crafts Alkylation (pp. 756-761) “S N 2” “S N 1”

9. Friedel-Crafts Acylation (pp. 756-761) Ph-CH 2 -R reduction Primary Not Rearranged!

10. Nucleophilic Aromatic Substitution (pp. 828-830) Backwards from S N 1 / S N 2

11.  H ‡ ~ 3 kcal/mol  H ‡ > 8 kcal/mol  H ‡ ~ 4 kcal/mol  H ‡ > 5 kcal/mol  H ‡ > 15 kcal/mol Allylic-Benzylic Reactivity - Cation (pp. 790 S N 1)

12. Allylic Reactivity - Cation (p. 705 kinetic-thermodynamic) CH 3 -CH-CH=CH 2  CH 3 -CH=CH-CH 2

13. End of Lecture 69 April 17, 2009