Electrophilic Aromatic Substitution

1. Electrophilic Aromatic Substitution Activating and Directing effects of substituents already on the ring

2. Products of Nitration 1 hr 48 hr 0.0003 hr

3. Mechanism of Electrophilic Aromatic Substitution With a substituent group G Depending on the nature of the substituent, the substituent G may stabilize the carbocation intermediate and therefore speed the reaction, or it may raise the energy of the carbocation and slow the reaction. Substituents that make the ring react faster (than benzene) with electrophiles are called activators; those that make the ring react slower (than benzene) are called deactivators.

4. Substituent effects • All activators also direct incoming electrophiles to the ortho- and the para-positions. • Most deactivators direct incoming electrophiles to the meta position. The exceptions are the halogens, which are weakly deactivating yet ortho-para directing.

5. Classification of Substituents

6. Product Distribution in Nitration (Percent %) (Percent %) XorthometaparaXorthometapara (meta-directing Deactivators)(ortho- and para-directing Deactivators) -N(CH3)3 2 89 11 -F 13 1 86 -NO2 7 91 2 -Cl 35 1 64 -CO2H 22 77 2 -Br 43 1 56 -CN 17 81 2 -I 45 1 54 -CO2CH2CH3 28 72 2(ortho- and para-directing Activators) -COCH3 26 72 2 -CH3 63 3 34 -CHO 19 72 9 -OH 50 0 50 -NHCOCH3 19 2 79

7. o,p-Activators (alkyl & aryl groups) 3º, especially stable 3º, especially stable

8. o,p-Activators with a lp of electrons o- 4 resonance forms m- p- 4 resonance forms

9. o,p-Deactivators (Halogens) o- 4 resonance forms m- p- 4 resonance forms

10. meta-directing Deactivators o- Especially UNSTABLE** m- p- Especially UNSTABLE**

11. Explanation of meta- deactivators • Meta directors slow the reaction by raising the energy of the carbocation intermediate because they have (in one resonance form, shown below) a positively charged atom attached to the ring. Two positively charged atoms so close together is very high in energy (especially unstable). nitro group sulfonic acid ketone nitrile

12. Summary of Substituent Effects • When the substituent is R (alkyl) or Ar (aryl), the resonance hybrid cation intermediate has three resonance forms. For attack of the electrophile at the ortho or parapositions, one of these is a 3º carbocation, which is especially stable. This lowers the energy of the intermediate, thus facilitates (speeds) the substitution reaction at the o- and p- positions. • When the substituent has a lone pair of electrons, such as the halogens, oxygen or nitrogen, the resonance hybrid for attack of the electrophile at the ortho and para positions has four resonance forms. This lowers the energy of the those intermediates, thus facilitates (speeds) the substitution reaction at the o- and p- positions.

13. Summary of Substituent Effects… • When the substituent has a multiple bond conjugated with the ring, and the second atom from the ring is more electronegative than the first, the substituent deactivates the ring and directs incoming electrophiles meta. It does this by raising the energy of the carbocation intermediates from ortho and para attack by an electrophile even more than it raises the energy of the intermediate resulting from meta attack.

14. Summary

15. Additivity of substituent effects in disubstituted aromatic rings • Rule 1: If the directing effects of two substituents reinforce each other, thepredicted product predominates. (o,p) (m)

16. Additivity of substituent effects… • Rule 2: If the directing effects of two substituents oppose each other, the more activating group dominates, but mixtures often result. (o,p; STRONG activator) (o,p; weak activator)

17. Additivity of substituent effects… • Rule 3: Substitution almost never occursbetween two substituents meta to each other. (o,p) X (too crowded) (o,p)

18. Additivity of substituent effects… • Rule 4: With a bulky o,p- director and/or a bulky electrophile, para substitution predominates. (o,p; BULKY) (HSO3+ is a BULKY electrophile)