12.12 Substituent Effects in Electrophilic Aromatic Substitution: Activating Substituents 8

Very strongly activating Strongly activating Activating 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 1

1. All activating substituents are ortho-para directors. 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. 23

Electron-Releasing Groups (ERGs) are ortho-para directing and activating ERG ERGs include —R, —Ar, and —C=C 25

Electron-Releasing Groups (ERGs) are ortho-para directing and strongly activating ERG ERGs such as —OH, and —OR are strongly activating 25

occurs about 1000 times faster than nitration of benzene Nitration of Phenol occurs about 1000 times faster than nitration of benzene OH OH NO2 OH NO2 HNO3 + 44% 56% 26

Bromination of Anisole FeBr3 catalyst not necessary OCH3 OCH3 Br Br2 acetic acid 90% 26

Oxygen Lone Pair Stabilizes Intermediate OCH3 •• • H Br + OCH3 •• • •• H Br + OCH3 + H H H H H Br all atoms have octets 26

Electron-Releasing Groups (ERGs) • ERG ERGs with a lone pair on the atom directly attached to the ring are ortho-para directing and strongly activating 25

Examples O OH OR OCR ERG = NHCR O NH2 NHR NR2 •• OR • •• OCR • •• ERG = • • NHCR • O • NH2 • NHR • NR2 All of these are ortho-para directing and strongly to very strongly activating 25

Lone Pair Stabilizes Intermediates for ortho and para Substitution X + ERG H X + ERG comparable stabilization not possible for intermediate leading to meta substitution 26

12.13 Substituent Effects in Electrophilic Aromatic Substitution: Strongly Deactivating Substituents 8

ERGs Stabilize Intermediates for ortho and para Substitution X + ERG • H X + ERG • 26

—CF3 is a powerful EWG. It is strongly deactivating and meta directing Electron-withdrawing Groups (EWGs) Destabilize Intermediates for ortho and para Substitution EWG EWG X H H H + + H H H H H H X H —CF3 is a powerful EWG. It is strongly deactivating and meta directing 26

Many EWGs Have a Carbonyl Group Attached Directly to the Ring —CR —EWG = O —COH O —COR O —CCl All of these are meta directing and strongly deactivating 25

All of these are meta directing and strongly deactivating Other EWGs Include: —EWG = —NO2 —SO3H —C N All of these are meta directing and strongly deactivating 25

Nitration of Benzaldehyde CH O O2N CH O HNO3 H2SO4 75-84% 26

Problem 12.14(a); page 468 Cl CCl O CCl O Cl2 FeCl3 62% 26

Disulfonation of Benzene HO3S SO3 SO3H H2SO4 90% 26

Bromination of Nitrobenzene Fe 60-75% 26

F, Cl, Br, and I are ortho-para directing, but deactivating 12.14 Substituent Effects in Electrophilic Aromatic Substitution: Halogens F, Cl, Br, and I are ortho-para directing, but deactivating 8

Nitration of Chlorobenzene Cl NO2 Cl NO2 Cl NO2 Cl HNO3 + + H2SO4 30% 1% 69% The rate of nitration of chlorobenzene is about 30 times slower than that of benzene. 6

Nitration of Toluene vs. Chlorobenzene 42 2.5 58 Cl 0.029 0.029 0.009 0.009 0.137 15